Viral Myocarditis: Classification, Diagnosis, and Clinical Implications.

Myocarditis is an inflammatory disease of the myocardium with focal or diffuse involvement. Viral infections are the most common cause of myocarditis, especially in Western countries. A recent viral illness with gastroenteric or upper respiratory symptoms often precedes myocarditis. The absence of specific pathognomonic features in conjunction with the wide spectrum of clinical manifestations that range from subclinical cases to sudden cardiac death (SCD) makes myocarditis diagnosis particularly challenging. Moreover, myocarditis might represent a cause of initially unexplained dilated cardiomyopathy (DCM) and heart failure (HF), especially among children and young adults. Cardiac magnetic resonance imaging (CMR) is crucial for myocarditis diagnosis, because of its ability to detect interstitial edema during acute inflammation. Assessment of subepicardial or mid-myocardial fibrosis by late gadolinium enhancement (LGE) is typical for myocarditis. Cardiac arrhythmias are frequent events that may arise especially in more severe myocarditis cases. The most common form of arrhythmia is atrial fibrillation, followed by ventricular tachycardia. Documented arrhythmias have been reported more commonly with HIV myocarditis than other more common infections such as Adenovirus, Parvovirus B19, human Herpes virus 6, and Enterovirus. The mechanisms of arrhythmogenesis in myocardial inflammation are not fully understood; in the acute phase, the spectrum of arrhythmogenesis ranges from a direct effect on cardiomyocytes that leads to electrical instability and ion channel impairment to ischemia from coronary macro- or microvascular disease. In chronic myocarditis, instead, myocardial replacement with fibrosis promotes scar-mediated re-entrant ventricular arrhythmias. Observational data suggested the important role of CMR, with LGE being the strongest independent predictor of SCD, cardiac, and all-cause mortality. In acute myocarditis, the most common localization of subepicardial LGE dwells in the lateral wall. Patients with myocarditis that develop HF and arrhythmias usually show a larger LGE distribution involving several myocardial segments. Moreover, a mid-layer LGE in the interventricular septum is more frequent in acute myocarditis than in acute coronary syndromes cases. The risk of SCD in patients with wide areas of LGE is significant, and a shared decision-making approach is warranted. Nevertheless, there is no formal consensus about the extension of LGE to justify implantable cardioverter defibrillator (ICD) implantation in primary prevention.

Early diagnosis of cardiomyopathies by cardiac magnetic resonance. Overview of the main criteria.

Cardiomyopathies (CMPs) are diseases of the heart muscle. They include a variety of myocardial disorders that manifest with various structural and functional phenotypes and are frequently genetic. Myocardial disease caused by known cardiovascular causes (such as hypertension, ischemic heart disease, or valvular disease) should be distinguished from CMPs for classification and management purposes. Identification of various CMP phenotypes relies primarily upon echocardiographic evaluation. In selected cases, cardiac magnetic resonance imaging (CMR) or computed tomography may be useful to identify and localize fatty infiltration, inflammation, scar/fibrosis, focal hypertrophy, and better visualize the left ventricular apex and right ventricle.  CMR imaging has emerged as a comprehensive tool for the diagnosis and follow-up of patients with CMPs. The accuracy and reproducibility in evaluating cardiac structures, the unique ability of non-invasive tissue characterization and the lack of ionizing radiation, make CMR very attractive as a potential "all-in-one technique". Indeed, it provides valuable data to confirm or establish the diagnosis, screen subclinical cases, identify aetiology, establish the prognosis. Additionally, it provides information for setting a risk stratification (based on evaluation of proved independent prognostic factors as ejection fraction, end-systolic-volume, myocardial fibrosis) and follow-up. Last, it helps to monitor the response to the therapy. In this review, the pivotal role of CMR in the comprehensive evaluation of patients with CMP is discussed, highlighting the key features guiding differential diagnosis and the assessment of prognosis.

Incremental value of normal adenosine perfusion cardiac magnetic resonance: Long-term outcome.

BACKGROUND: The purpose of the study was to determine the long-term prognostic value of normal adenosine stress cardiac magnetic resonance imaging (CMR) in patients referred for evaluation of myocardial ischemia. METHODS: We reviewed 300 consecutive patients (age 65 ± 11 years, 74% male) with suspected or known coronary disease and normal wall motion who had undergone adenosine stress CMR negative for ischemia and scar. Most patients were at intermediate risk of coronary artery disease. The end points studied were all causes of mortality and major adverse cardiac events, including cardiac death, myocardial infarction, revascularization, and hospitalization for unstable angina. RESULTS: During a mean follow-up of 5.5 years (mean = 5.4 ± 1.1), 16 patients died because of various causes (cardiac death in 5 patients). Three patients had a nonfatal myocardial infarction, 7 patients were hospitalized for revascularization, and 11 were medically treated for unstable angina. The annual cardiac event rate was 1.3% (0.78% in the first 3 years and 1.9% between the fourth and sixth years). The predictors of major adverse cardiac events in a multivariate analysis model were as follows: advanced age (hazard ratio [HR] 1.15, 95% confidence interval [95% CI] 1.02-1.30), diabetes (HR 17.5, 95% CI 2.2-140), and the habit of smoking (HR 5.9, 95% CI 1.0-35.5). For all causes of mortality, the only predictor was diabetes (HR 11.4, 95% CI 1.76-74.2). Patients with normal stress CMR had an excellent outcome during the 3 years after the study. The cardiac event rate was higher between the fourth and sixth years. CONCLUSION: Over a 5.5-year period, a low event rate and excellent prognosis occurred in patients with normal adenosine stress CMR. Low- to intermediate-risk patients with a normal CMR are at low risk for subsequent cardiac events.

Cardioverter-defibrillator implantation in myeloma-associated cardiac amyloidosis.

A 62-year-old woman with multiple myeloma and light-chain amyloidosis with significant heart involvement developed an in-hospital cardiac arrest. After cardiopulmonary resuscitation, a stable sinus rhythm without any cerebral damage was restored, and the patient was admitted to the coronary care unit. A cardioverter-defibrillator was implanted, and it successfully intervened in two sustained ventricular tachycardia episodes and one ventricular fibrillation episode, which were recorded during hospitalization. After achieving discrete cardiac compensation, the patient was transferred to the emergency medicine department where she underwent chemotherapy for multiple myeloma. The patient died 40 days after admission from refractory heart failure. In the literature, there are studies that describe the use of cardioverter-defibrillator implantation in cardiac amyloidosis; however, at present, there is no evidence of a beneficial effect on survival with the use of this intervention. A high index of suspicion for amyloid heart disease and early diagnosis are critical to improving outcomes.

Multiple coronary artery thrombosis in 5,10-methylenetetrahydrofolate reductase gene mutation.

A 42-year-old man presented at our attention with chest pain. His cardiac risk factors were smoking habit and family history of coronary artery disease. At the ECG, a mild ST-segment elevation in the inferior leads was shown. A normal left ventricular function was demonstrated at the echocardiography. An emergency coronary angiography was performed, and an extensive thrombosis of the right coronary artery and midleft anterior descending coronary artery was visualized. A primary angioplasty with thrombus aspiration and direct stenting of both sites followed. Biochemical analysis revealed a high plasma homocysteine level with a homozygotic anomaly of the 5,10-methylenetetrahydrofolate reductase. Currently, a nine-month followup negative for cardiac events is recorded.

Contrast-enhanced magnetic resonance imaging guided decision making after primary percutaneous coronary intervention for acute ST-elevation inferior myocardial infarction.

Coronary occlusion of large epicardial branches leads to profound ischemia at the infarct core, resulting in simultaneous necrosis of myocytes and endothelial cells. This process leads to microvascular obstruction in the infarct core, described as the no-reflow region in basic studies and documented in humans by contrast-enhanced magnetic resonance imaging and ultrasound. After coronary occlusion, contrast-enhanced magnetic resonance identifies myocardial infarction as a hyperenhanced region containing a hypoenhanced core. There is growing interest in incorporating its assessment into the evaluation of acute myocardial infarction because it is the key in defining specific therapeutic strategies and in directing the interventional therapy. We report a rare case of right ventricular infarction where contrast-enhanced magnetic resonance produced detailed images of myocardial perfusion pattern and tissue damage and directed the treatment after acute myocardial infarction.

Myocardial infarction in the young: a sex-based comparison.

A relative paucity of information concerns the natural history, clinical features and coronary anatomy in young patients with acute myocardial infarction. In particular, there is a dearth of data relating to sex differences in young patients. The objective was to evaluate whether or not there are correlations between the clinical characteristics and the extent and localization of coronary artery lesions in young men compared with young women. The study population consisted of 1646 young patients (87% men, 13% women; mean age 39+/-5 years) with a first acute myocardial infarction admitted to one of the 125 coronary care units of Italy in a period of 3 years. Clinical data were collected. All patients underwent coronary angiography during hospitalization. Smoking, hypercholesterolemia and obesity were significantly more prevalent in men than in women; physical inactivity was significantly more prevalent among women. Hemodynamically significant coronary stenosis occurred in 82% of patients and were more frequent in men than in women (P<0.05). Women more frequently had single-vessel disease and no coronary lesions at all (58 vs. 47% and 24 vs. 9% women vs. men respectively, both P<0.05). Men more frequently had multivessel disease (38 vs. 13%, P<0.05). Significant stenosis mainly affected the left anterior descending artery (52%) with no gender-related difference; men more likely had lesions of the left circumflex or right coronary artery (P<0.05). In conclusion, young patients with a first acute myocardial infarction risk factors profile and extent of coronary artery lesions were significantly different between sexes.

Variability in extent of platelet function inhibition after administration of optimal dose of glycoprotein IIb/IIIa receptor blockers in patients undergoing a high-risk percutaneous coronary intervention.

The Ultegra Rapid Platelet Function Assay was used to measure the inhibition of platelet aggregation at baseline and 10 minutes and 8 hours after starting therapy in 114 patients undergoing high-risk percutaneous coronary intervention with the planned use of a glycoprotein IIb/IIIa inhibitor. The abciximab-treated patients received a 0.25 mg/kg bolus, followed by a 0.125 microg/kg/min infusion for 12 hours; the eptifibatide-treated patients received 2 boluses of 180 microg/kg administered 10 minutes apart, followed by a 2 microg/kg/min infusion for 24 hours; the tirofiban-treated patients received a 25 microg/kg bolus, followed by a 0.15 microg/kg/min infusion for 18 hours. Ten minutes after starting therapy, the mean level of platelet inhibition was 86 +/- 9% for abciximab, 92 +/- 6% for eptifibatide, and 95 +/- 5% for tirofiban (p <0.001); > or =95% platelet inhibition was achieved in 29% of the patients treated with abciximab, 44% of those receiving eptifibatide, and 68% of the those receiving tirofiban (p = 0.02). In conclusion, at the evaluated doses, tirofiban seemed to be the most effective drug in achieving "optimal" platelet inhibition very early after percutaneous coronary intervention.

Long-term prediction of mortality in elderly persons by dobutamine stress echocardiography.

BACKGROUND: Dobutamine stress echocardiography (DSE) was shown to provide incremental prognostic information. However, its role in the prediction of mortality in elderly persons is not well defined. We assessed the value of DSE in the prediction of mortality and hard cardiac events during long-term follow-up in patients older than 65 years. METHODS: We studied 1434 patients >65 years old (mean age 72 +/- 3 years) who underwent DSE for evaluation of coronary artery disease. Ischemia was defined as new or worsening wall motion abnormalities. Follow-up events were total mortality and hard cardiac events (cardiac mortality and nonfatal myocardial infarction). Multivariable Cox regression analysis was used to identify the independent predictors of follow-up events. RESULTS: Ischemia was detected in 675 patients (47%). Five hundred six patients (35%) had a normal study, and 253 (18%) had fixed wall motion abnormalities. During a mean follow-up of 6.5 years, 532 (37%) deaths occurred, of which 249 (17%) were due to cardiac causes. A nonfatal myocardial infarction occurred in 45 patients (3%). Independent predictors of all-cause mortality in a multivariate analysis model were age (hazard ratio [HR] 1.06; 95% confidence interval [CI], 1.05-1.08), male sex (HR 1.5; 95% CI, 1.2-1.8), hypertension (HR 1.2; 95% CI, 1.1-1.4), smoking (HR 1.3; 95% CI, 1.1-1.6), diabetes (HR 1.4; 95% CI, 1.1-1.8), rest wall motion abnormalities (HR 1.07; 95% CI, 1.06-1.09), and ischemia (HR 1.3; 95% CI, 1.1-1.6). Independent predictors of hard cardiac events were age (HR 1.07; 95% CI, 1.05-1.09), male sex (HR 1.3; 95% CI, 1.1-1.7), smoking (HR 1.3; 95% CI, 1.1-1.6), diabetes (HR 1.6; 95% CI, 1.2-2.2), rest wall motion abnormalities (HR 1.13; 95% CI, 1.12-1.16), and ischemia (HR 2.1; 95% CI, 1.5-2.8). CONCLUSION: DSE provides independent prognostic information to predict all-cause mortality and hard cardiac events in elderly patients.

Prognostic value of dobutamine stress echocardiography in patients with systemic hypertension and known or suspected coronary artery disease.

Currently, there are no outcome data to suggest an incremental value of stress echocardiography in the risk stratification of patients who have hypertension after controlling for the left ventricular mass index (LVMI). This study assessed the incremental value of dobutamine stress echocardiography (DSE) for the prediction of mortality rate and cardiac events in patients who have hypertension. We studied 596 patients who had hypertension (mean age 62 +/- 12 years; 382 men) and who underwent DSE for evaluation of known or suspected coronary artery disease. End points during follow-up were hard cardiac events (cardiac death and nonfatal myocardial infarction) and total mortality rate. Left ventricular hypertrophy was detected by echocardiography in 119 patients (20%). During a median follow-up of 3 years, 101 patients (17%) died (43 cardiac deaths) and 19 patients had nonfatal myocardial infarction. In an incremental multivariate analysis model, clinical predictors of hard cardiac events were age, history of congestive heart failure, and LVMI. The percentage of abnormal myocardial segments examined with DSE was incremental to the clinical model (chi square 41 vs 27, p <0.001). Clinical predictors of total mortality rate were age, smoking, hypercholesterolemia, history of congestive heart failure, and LVMI. The peak wall motion score index was incremental to the clinical model (chi square 45 vs 40, p <0.05). DSE provides incremental data for the prediction of mortality rate and hard cardiac events in patients who have hypertension after adjustment for clinical data and LVMI.

Screening for left ventricular dysfunction using a hand-carried cardiac ultrasound device.

BACKGROUND: The hand-carried cardiac ultrasound (HCU) device is a recently introduced imaging device, which may be potentially useful in the primary care setting. AIM: To test the screening potential of a HCU for the detection of left ventricular (LV) dysfunction by evaluating LV ejection fraction (LVEF) and inferior vena cava (IVC) collapse. Standard echocardiographic system (SE) and plasma brain natriuretic peptide (BNP) measurements were used as a reference. METHODS: Eighty-eight consecutive patients (56 male, aged 59+/-12 years) with suspected LV dysfunction were enrolled in the study. The HCU-LVEF was visually estimated and the SE-LVEF was derived by the Simpson's biplane method. A LVEF <40% represented LV dysfunction. An IVC collapse of <50% and BNP levels > or =15 pmol/l were considered abnormal. The correlation of HCU-LVEF, HCU-IVC and BNP to the SE-LVEF and SE-IVC was analysed independently using 2x2 tables. RESULTS: Six patients were excluded because of poor echo images. 19/82 patients had LV dysfunction. The HCU and BNP could identify 17 and 18 out of these 19 patients, respectively. The agreement for LVEF and IVC collapse between SE and HCU was 96% for both parameters. The sensitivity of IVC collapse, HCU-LVEF and BNP in identifying patients with LV dysfunction was 26, 89 and 94%, respectively. CONCLUSION: A HCU device can reliably be used as a screening tool for LV dysfunction.