Afshin Farzaneh-Far

Cardiovascular Magnetic Resonance in Patients With Myocardial Infarction : Current and Emerging Applications

In patients with known or suspected myocardial infarction (MI), cardiovascular magnetic resonance (CMR) provides a comprehensive, multifaceted view of the heart. The data, including that from a recent multicenter clinical trial, indicate that delayed-enhancement cardiac magnetic resonance imaging (DE-CMR) is a well-validated, robust technique that can be easily implemented on scanners that are commonly available worldwide, with an effectiveness that clearly rivals the best available imaging techniques for the detection and assessment of acute and chronic MI. When patients present outside the diagnostic window of cardiac troponins, DE-CMR may be especially useful. Moreover, because DE-CMR can uniquely differentiate between ischemic and various nonischemic forms of myocardial injury, it may be helpful in cases of diagnostic uncertainty, such as in patients with classical features of MI in whom coronary angiography does not show a culprit lesion. Even after the diagnosis of MI has been made, CMR provides clinically relevant information by identifying residual viability, microvascular damage, stunning, and right ventricular infarction. In addition, post-MI sequelae, including left ventricular thrombus and pericarditis, are easily identified. Given that quantification of infarct size by DE-CMR is highly reproducible, this technique may provide a useful surrogate end point for clinical trials with appreciable reductions in sample size compared with alternative methods.

Vascular and valvar calcification: recent advances

The last few years have seen a surge of interest in the measurement of coronary artery calcification to predict and monitor the presence of coronary atherosclerosis. In addition, the rising clinical burden of valvar calcification in the aging population has highlighted the importance of understanding the processes of calcification within vascular tissues. Vascular calcification occurs in both the intima and the media of arteries, and there is evidence that these two sites of calcification are distinct entities (table 1). Intimal calcification only occurs within atherosclerotic plaques and is seen as early as the second decade of life, just after the fatty streak stage.1 In contrast, medial calcification occurs independently of intimal calcification and atherosclerosis. It commonly occurs in the peripheral arteries of the lower limbs in otherwise healthy elderly patients (Monckebergs sclerosis), where it is seen as “rail tracking” on plain radiographs. However, it also occurs in younger patients with diabetes and chronic renal failure. In diabetic patients, medial calcification appears to be a strong independent predictor of cardiovascular mortality and occurs particularly in those with neuropathy.2 Its presence can make palpating pulses and hearing Korotkoff sounds difficult and can lead to false elevation of cuff systolic blood pressure measurements. It also causes problems with the surgical management of vascular shunts. View this table: Table 1 Characteristics of intimal versus medial calcification More importantly, arterial wall stiffness has been shown to be correlated independently with aortic calcification.3 In theory this increased arterial stiffness from calcification may lead to an increase in cardiac work. In addition the reduction in aortic compliance may result in a decrease in diastolic coronary perfusion, as this is dependent on the recoil of the aorta which has been stretched during systole.4 Furthermore, increased arterial stiffness leads to an increase in pulse pressure, which is a highly significant …

Measuring myocardial scar by CMR.

Late gadolinium enhancement (LGE) using cardiac magnetic resonance (CMR) has emerged as the gold-standard technique for imaging of myocardial scar. The basic principle is inversion-recovery imaging after a 5- to 10-min delay following intravenous administration of gadolinium contrast ([1][1]). With

Idiopathic ventricular outflow tract tachycardia

Although the pathogenesis of ventricular outflow tract tachycardia has not been fully elucidated, recent findings suggest that defects in cAMP signalling may be involved

Impact of cardiovascular magnetic resonance on management and clinical decision-making in heart failure patients

BackgroundCardiovascular magnetic resonance (CMR) can provide important diagnostic and prognostic information in patients with heart failure. However, in the current health care environment, use of a new imaging modality like CMR requires evidence for direct additive impact on clinical management. We sought to evaluate the impact of CMR on clinical management and diagnosis in patients with heart failure.MethodsWe prospectively studied 150 consecutive patients with heart failure and an ejection fraction ≤50% referred for CMR. Definitions for “significant clinical impact” of CMR were pre-defined and collected directly from medical records and/or from patients. Categories of significant clinical impact included: new diagnosis, medication change, hospital admission/discharge, as well as performance or avoidance of invasive procedures (angiography, revascularization, device therapy or biopsy).ResultsOverall, CMR had a significant clinical impact in 65% of patients. This included an entirely new diagnosis in 30% of cases and a change in management in 52%. CMR results directly led to angiography in 9% and to the performance of percutaneous coronary intervention in 7%. In a multivariable model that included clinical and imaging parameters, presence of late gadolinium enhancement (LGE) was the only independent predictor of “significant clinical impact” (OR 6.72, 95% CI 2.56-17.60, p=0.0001).ConclusionsCMR made a significant additive clinical impact on management, decision-making and diagnosis in 65% of heart failure patients. This additive impact was seen despite universal use of prior echocardiography in this patient group. The presence of LGE was the best independent predictor of significant clinical impact following CMR.

Ischemia change in stable coronary artery disease is an independent predictor of death and myocardial infarction

OBJECTIVES The aim of this study was to evaluate the independent prognostic significance of ischemia change in stable coronary artery disease (CAD). BACKGROUND Recent randomized trials in stable CAD have suggested that revascularization does not improve outcomes compared with optimal medical therapy (MT). In contrast, the nuclear substudy of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial found that revascularization led to greater ischemia reduction and suggested that this may be associated with improved unadjusted outcomes. Thus, the effects of MT versus revascularization on ischemia change and its independent prognostic significance requires further investigation. METHODS From the Duke Cardiovascular Disease and Nuclear Cardiology Databanks, 1,425 consecutive patients with angiographically documented CAD who underwent 2 serial myocardial perfusion single-photon emission computed tomography scans were identified. Ischemia change was calculated for patients undergoing MT alone, percutaneous coronary intervention, or coronary artery bypass grafting. Patients were followed for a median of 5.8 years after the second myocardial perfusion scan. Cox proportional hazards regression modeling was used to identify factors independently associated with the primary outcome of death or myocardial infarction (MI). Formal risk reclassification analyses were conducted to assess whether the addition of ischemia change to traditional predictors resulted in improved risk classification for death or MI. RESULTS More MT patients (15.6%) developed ≥5% ischemia worsening compared with those undergoing percutaneous coronary intervention (6.2%) or coronary artery bypass grafting (6.7%) (p < 0.001). After adjustment for established predictors, ≥5% ischemia worsening remained a significant independent predictor of death or MI (hazard ratio: 1.634; p = 0.0019) irrespective of treatment arm. Inclusion of ≥5% ischemia worsening in this model resulted in significant improvement in risk classification (net reclassification improvement: 4.6%, p = 0.0056) and model discrimination (integrated discrimination improvement: 0.0062, p = 0.0057). CONCLUSIONS In stable CAD, ischemia worsening is an independent predictor of death or MI, resulting in significantly improved risk reclassification when added to previously known predictors.

Left atrial passive emptying function during dobutamine stress MR imaging is a predictor of cardiac events in patients with suspected myocardial ischemia.

OBJECTIVES The aim of this study was to determine the prognostic value of assessing left atrial function during dobutamine stress testing. BACKGROUND Left ventricular diastolic dysfunction precedes systolic wall motion abnormalities in the ischemic cascade. Severity of left ventricular diastolic function during cardiac stress is not characterized well by current clinical imaging protocols but may be an important prognostic factor. We hypothesized that abnormal early left atrial emptying measured during dobutamine stress cardiac magnetic resonance will reflect these diastolic changes and may be associated with cardiovascular outcomes. METHODS We enrolled 122 consecutive patients referred for dobutamine stress cardiac magnetic resonance for suspected myocardial ischemia. Left atrial volumes were retrospectively measured by the biplane area-length method at left ventricular end-systole (VOL(max)) and before atrial contraction (VOL(bac)). Left atrial passive emptying fraction defined by (VOL(max) - VOL(bac)) × 100%/VOL(max) and the absolute percent increase in left atrial passive emptying fraction during dobutamine stress (ΔLAPEF) were quantified. RESULTS Twenty-nine major adverse cardiac events (MACE) occurred during follow-up (median 23 months). By Kaplan-Meier analysis, patients with ΔLAPEF <10.8 (median) experienced higher incidence of MACE than did patients with a ΔLAPEF >10.8 (p = 0.004). By univariable analysis, ΔLAPEF was strongly associated with MACE (unadjusted hazard ratio for every 10% decrease = 1.56, p < 0.005). By multivariable analysis, every 10% decrease in ΔLAPEF carried a 57% increase in MACE, after adjustment to presence of myocardial ischemia and infarction. CONCLUSIONS Reduced augmentation of left atrial passive emptying fraction during dobutamine stress demonstrated strong association with MACE. We speculate that reduced left atrial passive emptying reserve during inotropic stress may represent underlying diastolic dysfunction and warrants further investigation.

Role of Mitochondrial Oxidative Stress in Glucose Tolerance, Insulin Resistance, and Cardiac Diastolic Dysfunction

Background Diabetes mellitus (DM) is associated with mitochondrial oxidative stress. We have shown that myocardial oxidative stress leads to diastolic dysfunction in a hypertensive mouse model. Therefore, we hypothesized that diabetes mellitus could cause diastolic dysfunction through mitochondrial oxidative stress and that a mitochondria‐targeted antioxidant (MitoTEMPO) could prevent diastolic dysfunction in a diabetic mouse model. Methods and Results C57BL/6J mice were fed either 60 kcal % fat diet (high‐fat diet [HFD]) or normal chow (control) for 8 weeks with or without concurrent MitoTEMPO administration, followed by in vivo assessment of diastolic function and ex vivo studies. HFD mice developed impaired glucose tolerance compared with the control (serum glucose=495±45 mg/dL versus 236±30 mg/dL at 60 minutes after intraperitoneal glucose injection, P<0.05). Myocardial tagged cardiac magnetic resonance imaging showed significantly reduced diastolic circumferential strain (Ecc) rate in the HFD mice compared with controls (5.0±0.3 1/s versus 7.4±0.5 1/s, P<0.05), indicating diastolic dysfunction in the HFD mice. Systolic function was comparable in both groups (left ventricular ejection fraction=66.4±1.4% versus 66.7±1.2%, P>0.05). MitoTEMPO‐treated HFD mice showed significant reduction in mitochondria reactive oxygen species, S‐glutathionylation of cardiac myosin binding protein C, and diastolic dysfunction, comparable to the control. The fasting insulin levels of MitoTEMPO‐treated HFD mice were also comparable to the controls (P>0.05). Conclusions MitoTEMPO treatment prevented insulin resistance and diastolic dysfunction, suggesting that mitochondrial oxidative stress may be involved in the pathophysiology of both conditions.

Biology of vascular calcification in renal disease.

The high rates of atherosclerotic vascular disease in patients with end-stage renal disease (ESRD) cannot be fully explained by the excess of traditional risk factors. Interest has therefore arisen in the possible role of vascular calcification, which is increased in these patients and may effect plaque stability and have detrimental hemodynamic consequences. Considerable evidence has accumulated recently pointing to the regulated nature of the calcification process. The initiation of calcium crystal formation appears to require the presence of small membrane bound vesicles released by living or apoptotic cells. The cellular release, content and phagocytosis of these vesicles appear to be important regulatory pathways in vascular calcification. Better understanding of these mechanisms may have therapeutic potential in reducing the adverse cardiovascular event rates in patients with (ESRD).

Accelerated atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus

It is important for primary care physicians to recognise rheumatoid arthritis and systemic lupus erythematosus patients as high‐risk groups for atherosclerosis, requiring aggressive risk‐factor modification. Recent studies suggest that this increased risk is not explained by an excess of traditional risk factors, but rather appears to be related to underlying rheumatic disease activity. Moreover, there is emerging data that aggressive treatment with disease‐modifying agents may reduce the incidence of atherosclerosis in these conditions.