Karolina M. Zareba

Myocardial fibrosis quantified by extracellular volume is associated with subsequent hospitalization for heart failure, death, or both across the spectrum of ejection fraction and heart failure stage

Background Myocardial fibrosis (MF) in noninfarcted myocardium may be an interstitial disease pathway that confers vulnerability to hospitalization for heart failure, death, or both across the spectrum of heart failure and ejection fraction. Hospitalization for heart failure is an epidemic that is difficult to predict and prevent and requires potential therapeutic targets associated with outcomes. Method and Results We quantified MF with cardiovascular magnetic resonance extracellular volume fraction (ECV) measures in 1172 consecutive patients without amyloidosis or hypertrophic or stress cardiomyopathy and assessed associations with outcomes using Cox regression. ECV ranged from 16.6% to 47.8%. Over a median of 1.7 years, 111 patients experienced events after cardiovascular magnetic resonance, 55 had hospitalization for heart failure events, and there were 74 deaths. ECV was more strongly associated with outcomes than “nonischemic” MF observed with late gadolinium enhancement, thus ECV quantified MF in multivariable models. Adjusting for age, sex, renal function, myocardial infarction size, ejection fraction, hospitalization status, and heart failure stage, higher ECV was associated with hospitalization for heart failure (hazard ratio 1.77; 95% CI 1.32 to 2.36 for every 5% increase in ECV), death (hazard ratio 1.87 95% CI 1.45 to 2.40) or both (hazard ratio 1.85, 95% CI 1.50 to 2.27). ECV improved classification of persons at risk and improved model discrimination for outcomes (eg, hospitalization for heart failure: continuous net reclassification improvement 0.33, 95% CI 0.05 to 0.66; P=0.02; 0.16, 95% CI 0.01 to 0.33; P=0.02; integrated discrimination improvement 0.037, 95% CI 0.008 to 0.073; P<0.01). Conclusion MF measured by ECV is associated with hospitalization for heart failure, death, or both. MF may represent a principal phenotype of cardiac vulnerability that improves risk stratification. Because MF can be reversible, cells and enzymes regulating collagen could be potential therapeutic targets.

Free-Breathing, Motion-Corrected Late Gadolinium Enhancement Is Robust and Extends Risk Stratification to Vulnerable Patients

Background— Routine clinical use of novel free-breathing, motion-corrected, averaged late-gadolinium-enhancement (moco-LGE) cardiovascular MR may have advantages over conventional breath-held LGE (bh-LGE), especially in vulnerable patients. Methods and Results— In 390 consecutive patients, we collected bh-LGE and moco-LGE with identical image matrix parameters. In 41 patients, bh-LGE was abandoned because of image quality issues, including 10 with myocardial infarction. When both were acquired, myocardial infarction detection was similar (McNemar test, P=0.4) with high agreement (&kgr;=0.95). With artifact-free bh-LGE images, pixelwise myocardial infarction measures correlated highly (R 2=0.96) without bias. Moco-LGE was faster, and image quality and diagnostic confidence were higher on blinded review (P<0.001 for all). During a median of 1.2 years, 20 heart failure hospitalizations and 18 deaths occurred. For bh-LGE, but not moco-LGE, inferior image quality and bh-LGE nonacquisition were linked to patient vulnerability confirmed by adverse outcomes (log-rank P<0.001). Moco-LGE significantly stratified risk in the full cohort (log-rank P<0.001), but bh-LGE did not (log-rank P=0.056) because a significant number of vulnerable patients did not receive bh-LGE (because of arrhythmia or inability to hold breath). Conclusions— Myocardial infarction detection and quantification are similar between moco-LGE and bh-LGE when bh-LGE can be acquired well, but bh-LGE quality deteriorates with patient vulnerability. Acquisition time, image quality, diagnostic confidence, and the number of successfully scanned patients are superior with moco-LGE, which extends LGE-based risk stratification to include patients with vulnerability confirmed by outcomes. Moco-LGE may be suitable for routine clinical use.

Myocardial Damage Detected by Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Is Associated With Subsequent Hospitalization for Heart Failure

Background Hospitalization for heart failure (HHF) is among the most important problems confronting medicine. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) robustly identifies intrinsic myocardial damage. LGE may indicate inherent vulnerability to HHF, regardless of etiology, across the spectrum of heart failure stage or left ventricular ejection fraction (LVEF). Methods and Results We enrolled 1068 consecutive patients referred for CMR where 448 (42%) exhibited LGE. After a median of 1.4 years (Q1 to Q3: 0.9 to 2.0 years), 57 HHF events occurred, 15 deaths followed HHF, and 43 deaths occurred without antecedent HHF (58 total deaths). Using multivariable Cox regression adjusting for LVEF, heart failure stage, and other covariates, LGE was associated with first HHF after CMR (HR: 2.70, 95% CI: 1.32 to 5.50), death (HR: 2.13, 95% CI: 1.08 to 4.21), or either death or HHF (HR: 2.52, 95% CI: 1.49 to 4.25). Quantifying LGE extent yielded similar results; more LGE equated higher risks. LGE improved model discrimination (IDI: 0.016, 95% CI: 0.005 to 0.028, P=0.002) and reclassification of individuals at risk (continuous NRI: 0.40, 95% CI: 0.05 to 0.70, P=0.024). Adjustment for competing risks of death that shares common risk factors with HHF strengthened the LGE and HHF association (HR: 4.85, 95% CI: 1.40 to 16.9). Conclusions The presence and extent of LGE is associated with vulnerability for HHF, including higher risks of HHF across the spectrum of heart failure stage and LVEF. Even when LVEF is severely decreased, those without LGE appear to fare reasonably well. LGE may enhance risk stratification for HHF and may enhance both clinical and research efforts to reduce HHF through targeted treatment.

Anthracycline Cardiotoxicity How Do We Move From Diagnosis to Prediction

Anthracyclines remain an integral part of chemotherapy regimens in many adult and pediatric cancers but cause myocardial damage that may manifest as either subclinical decrements of left ventricular ejection function or overt cardiomyopathy. Anthracycline-related cardiotoxicity is dose-limiting, and the risks of congestive heart failure increase with higher cumulative doses, particularly above 500 mg/m2 in adults and 300 mg/m2 in pediatric patients.1–3 The cardiotoxic effects of anthracyclines may be enhanced by other treatments, including radiation or trastuzumab. Anthracyclines may also lower the threshold for developing cardiac damage associated with aging or comorbid conditions, such as hypertension and diabetes mellitus. As the number of cancer survivors continues to grow, the burden of anthracycline-related cardiac damage is higher than previously thought.4–6 Thus, there is a critical need to better define and quantify treatment-related cardiovascular toxicity. Currently, predictors of anthracycline cardiotoxicity used in standard practice are limited to clinical cardiac risk factors and estimates of left ventricular function by echocardiography or gated radionuclide scans.7 This is a limited approach, and there is a need to expand anthracycline risk assessment in an evidence-based manner, given significant advances in cardiac imaging. See Article by Jordan et al Cardiac magnetic resonance (CMR) has become the gold standard for quantifying cardiac function and provides comprehensive tissue characterization of myocardial edema, fibrosis, and other features comparable to direct biopsy examination.8 These may serve as early imaging biomarkers and be more predictive of anthracycline-related cardiac injury. The potential of CMR is to permit …

Myocardial fibrosis is associated with subsequent death and hospitalization for heart failure in obese adults

Cardiac imaging in obese adults poses significant technical challenges, yet the prognostic value of diffuse myocardial fibrosis in obese adults quantified with cardiovascular magnetic resonance (CMR) extracellular volume fraction (ECV) measures is unknown. This issue is important because obesity increases the risks of death and hospitalization for heart failure (HHF). Myocardial fibrosis measured in obese adults with ECV may indicate vulnerability to death and HHF.

Coronary Artery Disease Testing: Past, Present, and Future

E valuating coronary artery disease (CAD) begins with a pretest likelihood of disease determined from an individual’s history, examination, and available clinical data. Current practice may then proceed to stress testing to assay myocardial ischemia, invasive coronary angiography (ICA), or no testing guided by patient preferences. When ICA results are at odds with noninvasive findings, practitioners recognize the complementary information yielded by the respective diagnostic tests. Further, they recognize that the ideal management of CAD incorporates both anatomic (epicardial coronary stenosis) and physiologic (myocardial ischemia) information. Classically, this has required an ischemia test followed by ICA, or ICA followed by catheter-based hemodynamic assays such as fractional flow reserve (FFR). Compelling studies have shown, before the emergence of coronary angiography with noninvasive computed tomography (CTA), that a combined approach improves outcomes (2,3). The randomized PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial found comparable outcomes with CTA or stress testing in individuals referred for new CAD evaluation (4). Essentially, this trial looked at what happens after obtaining either anatomic or physiologic information. With the emergence of computational fluid dynamics–based methods to estimate FFR from CTA

The role of stress cardiac magnetic resonance in women

Coronary artery disease (CAD) is the leading cause of death in women. Nevertheless, extensive evidence demonstrates under-diagnosis and under-treatment of women for suspected or known ischemic heart disease (IHD). Stress cardiac magnetic resonance (CMR) is becoming readily available and offers significant advantages over other stress imaging modalities. The high spatial and temporal resolution of CMR provides the unique ability to identify subendocardial ischemia, viability, and the presence of microvascular disease. Furthermore, CMR is free from ionizing radiation, and image quality is not compromised by attenuation artifacts or patient size. Over the past two decades, evidence-based data have demonstrated the high diagnostic and prognostic performance of stress CMR in the context of IHD, often superior to other stress imaging techniques. Importantly, ad hoc studies confirmed these results in women with known or suspected IHD. Stress CMR warrants consideration as the modality of choice for women requiring an imaging test for ischemia given its strong evidence base, superior test characteristics, comprehensive nature, and unique ability to characterize both epicardial and microvascular disease.

MYOCARDIAL FIBROSIS QUANTIFIED BY CMR EXTRACELLULAR VOLUME FRACTION PREDICTS MORTALITY AND DETECTS RESPONSE TO THERAPY IN THE NONISCHEMIC PATIENT POPULATION

Myocardial fibrosis expands the extracellular matrix (ECM) adversely affecting mechanical, electrical, and vasomotor function. We quantified ECM expansion, evaluated its association with mortality in the non-ischemic patient population, and assessed the impact of renin angiotensin aldosterone system

T‐Wave Abnormality as Electrocardiographic Signature of Myocardial Edema in Non‐ST‐Elevation Acute Coronary Syndromes

Background T‐wave abnormalities are common during the acute phase of non‐ST‐segment elevation acute coronary syndromes, but mechanisms underlying their occurrence are unclear. We hypothesized that T‐wave abnormalities in the presentation of non‐ST‐segment elevation acute coronary syndromes correspond to the presence of myocardial edema. Methods and Results Secondary analysis of a previously enrolled prospective cohort of patients presenting with non‐ST‐segment elevation acute coronary syndromes was conducted. Twelve‐lead electrocardiography (ECG) and cardiac magnetic resonance with T2‐weighted imaging were acquired before invasive coronary angiography. ECGs were classified dichotomously (ie, ischemic versus normal/nonischemic) and nominally according to patterns of presentation: no ST‐ or T‐wave abnormalities, isolated T‐wave abnormality, isolated ST depression, ST depression+T‐wave abnormality. Myocardial edema was determined by expert review of T2‐weighted images. Of 86 subjects (65% male, 59.4 years), 36 showed normal/nonischemic ECG, 25 isolated T‐wave abnormalities, 11 isolated ST depression, and 14 ST depression+T‐wave abnormality. Of 30 edema‐negative subjects, 24 (80%) had normal/nonischemic ECGs. Isolated T‐wave abnormality was significantly more prevalent in edema‐positive versus edema‐negative subjects (41.1% versus 6.7%, P=0.001). By multivariate analysis, an ischemic ECG showed a strong association with myocardial edema (odds ratio 12.23, 95% confidence interval 3.65‐40.94, P<0.0001). Among individual ECG profiles, isolated T‐wave abnormality was the single strongest predictor of myocardial edema (odds ratio 23.84, 95% confidence interval 4.30‐132, P<0.0001). Isolated T‐wave abnormality was highly specific (93%) but insensitive (43%) for detecting myocardial edema. Conclusions T‐wave abnormalities in the setting of non‐ST‐segment elevation acute coronary syndromes are related to the presence of myocardial edema. High specificity of this ECG alteration identifies a change in ischemic myocardium associated with worse outcomes that is potentially reversible.

Cardiac Magnetic Resonance in Sudden Cardiac Arrest Survivors

Sudden cardiac arrest (SCA) is a major challenge in medicine despite significant advances in cardiology over the last few decades. Identification of causes of SCA has major implications for patient management, primary and secondary prevention of sudden cardiac death, and all-cause mortality. SCA predominantly affects individuals with underlying heart disease, especially ischemic heart disease occurring 6 to 9 times more often in postinfarction patients than in patients without myocardial infarction.1 In the landmark Maastricht Circulatory Arrest Registry,1 among 224 SCA victims, only 4% were because of an acute myocardial infarction but 92 of them (41%) had a prior myocardial infarction at a median of 9 years before SCA. Furthermore, the incidence of SCA is substantially increasing after the age of 65 years in males and later in females, coinciding with an increasing incidence of ischemic heart disease in this population.2 However, the incidence and risk of SCA in ischemic patients has decreased over the past 2 decades because of primary coronary intervention, widespread use of statins, and other contemporary medications.3 At the same time, the relative proportion of nonischemic causes of SCA is increasing and plays a particularly important role at the age <65 years.4,5 Ruling out coronary disease as a cause of SCA is an initial step of diagnosis, but subsequent differential diagnosis of nonischemic causes remains challenging. See Article by Rodrigues et al Cardiac magnetic resonance (CMR) …