Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry.

BACKGROUND: There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals. METHODS: A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance. RESULTS: At presentation, 118 patients (26.6%) had left ventricular ejection fraction <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). ß-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation. CONCLUSIONS: In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.

Timing and magnitude of regional right ventricular function: a speckle tracking-derived strain study of normal subjects and patients with right ventricular dysfunction.

BACKGROUND: The aim of this study was to evaluate the timing and magnitude of global and regional right ventricular (RV) function by means of speckle tracking-derived strain in normal subjects and patients with RV dysfunction. METHODS: Peak longitudinal systolic strain (PLSS) and time to PLSS in 6 RV segments (the basal, mid, and apical segments of the RV free wall and septum) were obtained in 100 healthy volunteers and 76 patients with RV dysfunction by tracking speckles inside the myocardium using grayscale images. Global PLSS and time to PLSS were based on the average of the 6 regional values. RESULTS: There was a significant and close correlation between RV contractility as measured by PLSS and tricuspid annular plane systolic excursion (r = -0.83, P < .001). In normal subjects, PLSS was significantly greater in the free wall than in the septum (-28.7 + or - 4.1% vs -19.8 + or - 3.4%, P < .001), whereas time to PLSS was similar in the different regions of the right ventricle. In patients with RV dysfunction, global and regional PLSS was significantly less than in normal subjects (-13.7 + or - 3.6% vs -24.2 + or - 2.9%, P < .001), and a global PLSS cutoff value of -19% was helpful in distinguishing the two groups. Furthermore, time to PLSS in all of the RV septal segments and dispersion in RV contraction timing were significantly longer. Global PLSS in the patients with RV dysfunction was also significantly less in the presence of moderate to severe pulmonary hypertension (-12.7 + or - 3.6% vs -14.4 + or - 3.4%, P = .038). CONCLUSIONS: Speckle tracking not only makes it possible to quantify global RV function but also illustrates the physiology of RV contraction and the pattern of activation at regional level. Speckle tracking-derived strain could become an important new means of assessing and following up patients with impaired RV function and increased pulmonary pressure.

Comparison of eight echocardiographic methods for determining the prevalence of mechanical dyssynchrony and site of latest mechanical contraction in patients scheduled for cardiac resynchronization therapy.

Prevalence of echocardiographically assessed mechanical dyssynchrony and consistency in detection of the latest mechanical left ventricular (LV) contracting region when different echocardiographic methods are used in the same patient remains ill-defined. The objectives of this study were to evaluate (1) the prevalence of intraventricular mechanical dyssynchrony and (2) consistency of latest mechanical LV contraction using a multiparametric approach derived from tissue Doppler imaging (TDI), 3-dimensional (3D) echocardiography, and speckle tracking in patients scheduled for cardiac resynchronization therapy (CRT). In 63 patients with heart failure scheduled for CRT, 2D echocardiography, TDI, 3D echocardiography, and speckle tracking were prospectively collected and analyzed. Prevalence of dyssynchrony was low for some tissue-velocity derived indexes (11%, 13%, and 43%) but was >or=80% for strain derived by TDI, for systolic dyssynchrony index by 3D echocardiography, and for longitudinal and radial strains by speckle tracking. Prevalence of dyssynchrony was 69% for maximum delay between anteroseptal and posterolateral walls by radial strain. Agreement among dyssynchrony indexes was generally low (kappa -0.02). Agreement of each of these echocardiographic indexes in determining, in the same patient with heart failure, the latest LV mechanical contraction site was also low (no site agreement in 77%). In conclusion, in a typical CRT population there is considerable variability among various techniques that assess prevalence of mechanical dyssynchrony and in identification of the latest mechanical LV contracting region.

Echocardiographic parameters of mechanical synchrony in healthy individuals.

Definition and validation of the ranges of normal values and agreement among echocardiographic measures of mechanical synchrony in healthy subjects are mostly lacking. The aims of this study were (1) to assess the ranges of normal values for 5 tissue Doppler imaging parameters, real-time 3-dimensional echocardiographic measures, and speckle-tracking measures of mechanical synchrony; (2) to evaluate interinstitutional variability; (3) to compare the ranges of normal values with those reported in previous research; and (4) to analyze the agreement among all parameters in the same healthy subject. Time to peak systolic velocity (Ts), the delay between Ts at the basal septal and lateral segments, peak velocity difference, strain derived by tissue Doppler imaging, Ts derived by tissue synchronization imaging, systolic synchrony index (SSI) derived by real-time 3-dimensional echocardiography, and longitudinal and radial strain derived by speckle tracking were prospectively collected and analyzed at 2 different institutions in 160 consecutive healthy subjects. The ranges of normal values, expressed as means +/- 2 SDs, were 30.32 +/- 29.36 ms for the SD of Ts, 15.51 +/- 99.88 ms for septal-lateral delay, 60.75 +/- 81.62 ms for peak velocity difference, 33.07 +/- 29.96 ms for tissue synchronization imaging, 34.16 +/- 23.26 ms for the SD of strain, 2.74 +/- 2.16% for SSI, 28.91 +/- 23.02 ms for the SD of longitudinal strain, and 10.4 +/- 6.31 ms for radial strain. There was large interinstitutional variability for all parameters. Three-dimensional SSI and radial strain were within the published upper range limit for healthy subjects. Ninety percent of healthy subjects were consistently classified to be synchronous by 1 parameter. With a composite index, more subjects than expected showed dyssynchrony (10% vs 2.5%). In conclusion, 3-dimensional SSI and radial strain were the most reproducible parameters and consistently discriminated normal healthy subjects from the cardiac resynchronization therapy volume responders.

Influence of left atrial and ventricular volumes on the relation between mitral valve annulus and coronary sinus.

The aim of this study was to evaluate the anatomic relation between the coronary sinus (CS), mitral annulus, and coronary arteries using 64-multislice computed tomography (MSCT) in patients presenting with a wide range of atrial volumes and left ventricular functions to determine the potential clinical use for percutaneous mitral annuloplasty (PMA). The MSCT data of 165 patients (age 63.65 +/- 12.89 years, 67.3% men) were evaluated. The following variables were measured: CS length, CS ostium area, area of the section of CS when it becomes great cardiac vein, area between CS and atrioventricular groove assessed in volume-rendered 3-dimensional images, axial angle measured as the angle between CS and mitral annulus assessed in axial section, mitral valve annulus (MVA) area, left atrium volume, and left circumflex artery/marginal branch-CS relation referring to mitral annulus. The correlation was inversed between the reduction of the axial angle and all following variables: enlargement of both left ventricular end-systolic (r = -0.429, p <0.001) and end-diastolic (r = -0.428, p <0.001) volumes, left atrial volume (r = -0.361, p <0.001), and MVA (r = -0.324, p <0.001). Similarly, there was inverse correlation between the reduction of the area between CS and atrioventricular groove, and enlargement of both left ventricular end-systolic (r = -0.376, p <0.001) and end-diastolic (r = -0.291, p <0.001) volumes, left atrial volume (r = -0.221, p = 0.001), and MVA (r = -0.155, p = 0.019). Of note, circumflex artery was located between CS and MVA in 77% of the patients, but in patients with severe mitral regurgitation CS crossed circumflex/marginal branch artery more frequently (97% of cases). In conclusion, a close proximity of the CS to the mitral annulus but also to circumflex artery is more likely to occur with left atrial and ventricular enlargement. Thus, MSCT should be considered as part of the selection process of potential candidate to PMA to avoid external compression of circumflex artery/marginal branch by the device.

Quantitative analysis of intraventricular dyssynchrony using wall thickness by multidetector computed tomography.

OBJECTIVES: We sought to determine the feasibility of cardiac computed tomography (CT) to detect significant differences in the extent of left ventricular dyssynchrony in heart failure (HF) patients with wide QRS, HF patients with narrow QRS, and age-matched controls. BACKGROUND: The degree of mechanical dyssynchrony has been suggested as a predictor of response to cardiac resynchronization therapy. There have been no published reports of dyssynchrony assessment with the use of CT. METHODS: Thirty-eight subjects underwent electrocardiogram-gated contrast-enhanced 64-slice multidetector CT. The left ventricular endocardial and epicardial boundaries were delineated from short-axis images reconstructed at 10% phase increments of the cardiac cycle. Global and segmental CT dyssynchrony metrics that used changes in wall thickness, wall motion, and volume over time were assessed for reproducibility. We defined a global metric using changes in wall thickness as the dyssynchrony index (DI). RESULTS: The DI was the most reproducible metric (interobserver and intraobserver intraclass correlation coefficients >/=0.94, p < 0.0001) and was used to determine differences between the 3 groups: HF-wide QRS group (ejection fraction [EF] 22 +/- 8%, QRS 163 +/- 28 ms), HF-narrow QRS (EF 26 +/- 7%, QRS 96 +/- 11 ms), and age-matched control subjects (EF 64 +/- 5%, QRS 87 +/- 9 ms). Mean DI was significantly different between the 3 groups (HF-wide QRS: 152 +/- 44 ms, HF-narrow QRS: 121 +/- 58 ms, and control subjects: 65 +/- 12 ms; p < 0.0001) and greater in the HF-wide QRS (p < 0.0001) and HF-narrow QRS (p = 0.005) groups compared with control subjects. We found that DI had a good correlation with 2-dimensional (r = 0.65, p = 0.012) and 3-dimensional (r = 0.68, p = 0.008) echocardiographic dyssynchrony. CONCLUSIONS: Quantitative assessment of global CT-derived DI, based on changes in wall thickness over time, is highly reproducible and renders significant differences between subjects most likely to have dyssynchrony and age-matched control subjects.

Tomographic left ventricular volumetric emptying analysis by real-time 3-dimensional echocardiography: influence of left ventricular dysfunction with and without electrical dyssynchrony.

BACKGROUND: The sequence of left ventricular (LV) systolic emptying is not completely understood. Using real-time 3-dimensional echocardiography, we investigated this sequence and LV synchronicity in physiological and pathological conditions. METHODS AND RESULTS: The study population consisted of 116 healthy volunteers, 20 top-level athletes, 35 patients with LV dysfunction, and 84 patients with LV dysfunction and left bundle-branch block (LBBB). We subdivided the LV into 16 volumetric segments for regional analysis and into apical, middle, and basal regions to calculate the mean of end-systolic times and the time to minimum systolic volume of each region. In healthy volunteers and in top-level athletes, the emptying systolic times increased smoothly from apex to base. These differences determined an apex-to-base time gradient in the LV emptying sequence. In patients with LV dysfunction and without LBBB, this gradient was maintained with a relatively higher LV dyssynchrony. However, in patients with LV dysfunction and LBBB, there was no clear sequence in LV emptying volumes, and this group had the highest LV dyssynchrony. CONCLUSIONS: Real-time 3-dimensional echocardiography tomographic slicing of the LV enables accurate analysis of LV emptying in physiological conditions and in conditions of LV dysfunction with and without electrical dyssynchrony. Progressive dilation of LV produces deterioration in LV synchronicity. However, it is the presence of LV dysfunction in combination with LBBB that determines the loss of the apex-to-base time gradient in LV emptying.

Coronary sinus visualization by 3-dimensional real-time echocardiography.

BACKGROUND: Real-time 3-dimensional echocardiography (RT3DE) to visualize the coronary sinus (CS) was compared with multislice cardiac tomography (MSCT). METHODS: In all, 37 consecutive patients undergoing MSCT received RT3DE a few hours later. Group A (n = 22) had normal left ventricular dimension/function, whereas group B (n = 15) had heart failure. RESULTS: The CS could be visualized in both groups (91% and 93%) with a significantly larger diameter in B. Systolic CS diameter was always larger than diastolic, but patients with heart failure showed significantly less difference (7.6% +/- 4.2% vs 12.2% +/- 6.1%, P < .05). When systolic and diastolic measurements were possible, MSCT and RT3DE agreed (Lin R = -0.09 [95% confidence interval 0.73-0.93]) but less so from the proximal to mid/distal segments (Lin R 0.90, 0.61, 0.41, respectively). Observers learned the procedure in approximately 5 minutes. CONCLUSION: The CS can be visualized and quantitatively assessed by RT3DE in an easily learned procedure that agrees with MSCT results, especially in patients with heart failure.

Role of multislice computed tomography for preprocedural evaluation before revision of a chronically implanted transvenous left ventricular lead.

The purpose of this study was to determine the feasibility of multislice computed tomography (MSCT) to assess the coronary sinus (CS) and its tributaries in patients who are undergoing cardiac resynchronization therapy and need a left ventricular (LV) lead revision. Preprocedural imaging modality, which may enable delineation of the cardiac venous anatomy in patients who need LV lead replacement, has not yet been evaluated. Ten patients with heart failure with previously implanted cardiac resynchronization therapy devices, who presented with worsening heart failure, were studied with MSCT and tissue Doppler imaging echocardiography before LV lead replacement. MSCT was performed to evaluate patency of the CS and coronary veins, and tissue Doppler imaging echocardiography assessed the region and the magnitude of mechanical dyssynchrony. An excellent concordance in the vein diameter, location, and status between MSCT and angiography was found. Apart from the need to perform a venoplasty in 1 patient and an unsuccessful lead explantation in another patient, all other anatomic issues were correctly predicted by MSCT. CS or vein occlusion were present in 4 patients, and in 3 of them surgical LV lead replacement was performed. Identification of a patent venous system enabling successful transvenous lead implantation was possible in 2 patients. Direct visualization of the proximity of the target vein to the phrenic nerve and the diaphragm guided lead selection and position in 4 patients. In conclusion, MSCT may be used to delineate the coronary venous anatomy in patients in whom LV lead replacement is needed to help strategize whether a transvenous or transthoracic approach may be preferred for LV lead revision.

Exercise hyperpnea in chronic heart failure: relationships to lung stiffness and expiratory flow limitation.

The changes in breathing pattern and lung mechanics in response to incremental exercise were compared in 14 subjects with chronic heart failure and 15 normal subjects. In chronic heart failure subjects, exercise hyperpnea was achieved by increasing breathing frequency more than tidal volume. The rate of increase in breathing frequency with carbon dioxide output was inversely correlated (r = -0.61, P < 0.05) with dynamic lung compliance measured at rest, but not with static lung compliance either at rest or at maximum exercise. Although decrease in expiratory flow reserve near functional residual capacity in chronic heart failure occurred earlier with exercise than in the normal subjects (P < 0.01), it was not correlated with changes in breathing pattern or occurrence of tachypnea. Tachypnea was achieved in chronic heart failure subjects with an increase in duty cycle because of a greater than normal decrease in expiratory time with exercise. We conclude that in chronic heart failure preexisting increase in lung stiffness plays a significant role in causing tachypnea during exercise. The results of the present study do not support the hypothesis that dynamic compression of the airways downstream from the flow-limiting segment occurring during exercise contributes to hyperpnea.