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BACKGROUND: The severity classification of functional mitral regurgitation (FMR) remains controversial despite adverse prognosis and rapidly evolving interventions. Furthermore, it is unclear if quantitative assessment with cardiac magnetic resonance can provide incremental risk stratification for patients with ischemic cardiomyopathy (ICM) or non-ICM (NICM) in terms of FMR and late gadolinium enhancement (LGE). We evaluated the impact of quantitative cardiac magnetic resonance parameters on event-free survival separately for ICM and NICM, to assess prognostic FMR thresholds and interactions with LGE quantification. METHODS: Patients (n=1414) undergoing cardiac magnetic resonance for cardiomyopathy (ejection fraction<50%) assessment from April 1, 2001 to December 31, 2017 were evaluated. The primary end point was all-cause death, heart transplant, or left ventricular assist device implantation during follow-up. Multivariable Cox analyses were conducted to determine the impact of FMR, LGE, and their interactions with event-free survival. RESULTS: There were 510 primary end points, 395/782 (50.5%) in ICM and 114/632 (18.0%) in NICM. Mitral regurgitationfraction per 5% increase was independently associated with the primary end point, hazards ratios (95% CIs) of 1.04 (1.01-1.07; P=0.034) in ICM and 1.09 (1.02-1.16; P=0.011) in NICM. Optimal mitral regurgitation-fraction threshold for moderate and severe FMR were =20% and =35%, respectively, in both ICM and NICM, based on the prediction of the primary outcome. Similarly, optimal LGE thresholds were =5% in ICM and =2% in NICM. Mitral regurgitation-fraction×LGE emerged as a significant interaction for the primary end point in ICM (P=0.006), but not in NICM (P=0.971). CONCLUSIONS: Mitral regurgitation-fraction and LGE are key quantitative cardiac magnetic resonance biomarkers with differential associations with adverse outcomes in ICM and NICM. Optimal prognostic thresholds may provide important clinical risk prognostication and may further facilitate the ability to derive selection criteria to guide therapeutic decision-making. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cardiomyopathies with increased left ventricular wall thickness such as cardiac amyloidosis, septal hypertrophic cardiomyopathy (HCM), and apical HCM exhibit characteristic regional longitudinal strain (LS) patterns. However, between-vendor agreement of segmental and regional LS has not been tested in these diseases. We sought to assess LS values among vendors in specific cardiomyopathies that exhibit regional strain variation: cardiac amyloidosis, septal HCM, and apical HCM. METHODS: This was a prospective, cross-sectional study of 69 patients (18 amyloidosis, 30 septal HCM, 6 apical HCM, and 15 controls) who underwent clinically indicated outpatient echocardiography at the Cleveland Clinic. Peak systolic segmental, regional (basal, mid, and apical), and global LS were evaluated using GE (EchoPAC), Siemens (Velocity Vector Imaging), and Phillips (QLab) systems in the same imaging session. Between-vendor, differences were analyzed using correlation coefficients, Bland Altman plots, and a mixed model. RESULTS: Global LS was highly correlated among the 3 software packages and most abnormal in patients with amyloidosis (P<0.001). Regional LS analysis demonstrated that QLab software tended to produce more negative LS values, driven by differences in apical strains. EchoPAC had the greatest ability to discriminate patients with amyloidosis using regional strain values (area under the curve, 0.932) as compared with Velocity Vector Imaging and QLab (P<0.001). CONCLUSIONS: Global and regional variations in LS exist betweenvendors in patients with cardiomyopathies with increased left ventricular wall thickness (amyloidosis, septal HCM, and apical HCM). It is important to be aware of these differences for diagnosis, prognosis, and serial examinations in these conditions. [ABSTRACT FROM AUTHOR]

Background--In asymptomatic patients with ≥3+ mitral regurgitation and preserved left ventricular (LV) ejection fraction who underwent mitral valve surgery, we sought to discover whether baseline LV global longitudinal strain (LV-GLS) and brain natriuretic peptide provided incremental prognostic utility. Methods and Results--Four hundred and forty-eight asymptomatic patients (61±12 years and 69% men) with ≥3+ primary mitral regurgitation and preserved left ventricular ejection fraction, who underwent mitral valve surgery (92% repair) at our center between 2005 and 2008, were studied. Baseline clinical and echocardiographic data (including LV-GLS using Velocity Vector Imaging, Siemens, PA) were recorded. The Society of Thoracic Surgeons score was calculated. The primary outcome was death. Mean Society of Thoracic Surgeons score, left ventricular ejection fraction, mitral effective regurgitant orifice, indexed LV end-diastolic volume, and right ventricular systolic pressure were 4±1%, 62±3%, 0.55±0.2 cm², 58±13 cc/m², and 37±15 mm Hg, respectively. Forty-five percent of patients had flail. Median log-transformed BNP and LV-GLS were 4.04 (absolute brain natriuretic peptide: 60 pg/dL) and -20.7%. At 7.7±2 years, death occurred in 41 patients (9%; 0% at 30 days). On Cox analysis, a higher Society of Thoracic Surgeons score (hazard ratio 1.55), higher baseline right ventricular systolic pressure (hazard ratio 1.11), more abnormal LV-GLS (hazard ratio 1.17), and higher median log-transformed BNP (hazard ratio 2.26) were associated with worse longer-term survival (all P<0.01). Addition of LV-GLS and median log-transformed BNP to a clinical model (Society of Thoracic Surgeons score and baseline right ventricular systolic pressure) provided incremental prognostic utility (Χ2 for longer-term mortality increased from 31-47 to 61; P<0.001). Conclusions--In asymptomatic patients with significant primary mitral regurgitation and preserved left ventricular ejection fraction who underwent mitral valve surgery, brain natriuretic peptide and LV-GLS provided synergistic risk stratification, independent of established factors. [ABSTRACT FROM AUTHOR]

The decision-making role of exercise echocardiography in the surgical timing for aortic regurgitation remains a matter of debate because of limited data on its link with outcome. The aim of this study was to assess the role of echocardiographic measurements at rest and during exercise as predictors of valve surgery in asymptomatic aortic regurgitation.Comprehensive resting and exercise echocardiography was performed in 159 consecutive patients (50±15 years; 80% male) with isolated moderately severe to severe aortic regurgitation and preserved left ventricular (LV) function (LV ejection fraction >50%, LV end-diastolic dimension 70 mm, LV end-systolic dimension 50 mm or 25 mm/m2) in whom initial management was expectant. Echocardiographic measurements were performed at rest and during exercise. LV and right ventricular (RV) longitudinal strain was analyzed at rest using velocity vector imaging. Valve surgery was performed in 50 patients (31%) during 30±21 months. After adjustment for age and sex in a multivariable Cox proportional-hazards model, exercise tricuspid annular plane systolic excursion (TAPSE; hazards ratio [HR], 0.48; P=0.001) was associated with valve surgery-free, independent of resting LV strain (HR, 1.63; P=0.005), exercise LV end-diastolic volume (HR, 1.38; P=0.048), and resting RV strain (HR, 1.69; P=0.002). In sequential Cox models, a model based on clinical data (χ2, 20.4) was improved by resting LV strain (χ2, 30.1; P=0.001), resting RV strain (χ2, 49.7; P<0.001), and further increased by exercise TAPSE (χ2, 64.4; P<0.001).In asymptomatic aortic regurgitation, resting LV strain, resting RV strain, and exercise TAPSE were independently associated with the need for earlier aortic surgery. [ABSTRACT FROM AUTHOR]

Cervical vagal nerve stimulation (VNS) can improve left ventricular dysfunction in the setting of heart failure (HF). However, little is known about the impact of VNS on left atrial (LA) function. The aim of this study was to compare LA mechanics and histology between control and VNS-treated animals during HF development.Fifteen mongrel dogs were randomized into control (n=7) and VNS (n=8) groups. All dogs underwent 8 weeks of high-rate ventricular pacing (at 220 beats per minute for the first 4 weeks to develop HF and another 4 weeks at 180 beats per minute to maintain HF). LA contractile function (LA negative peak strain), conduit function (LA positive peak strain), and reservoir function (LA total strain) were measured from speckle tracking in 2 groups. At the end of the terminal study, the LA appendage was obtained. Baseline LA strains were comparable in the control and VNS-treated dogs. At 4 and 8 weeks of ventricular pacing, all LA strains were decreased and LA volumes were increased in the control group compared with the VNS group (P<0.05). Histological evaluation of the left atrium revealed that percent fibrosis was significantly lower in the VNS versus the control group (8±1% versus 13±1%; P<0.001). Finally, transmitral flow showed decreased atrial contribution to left ventricular filling in the control group (P<0.05).VNS improved LA function and volumes and suppressed LA fibrosis in the canine high-rate ventricular pacing model. VNS is a novel and potentially useful therapy for improving LA function during HF. [ABSTRACT FROM AUTHOR]

The aim of our study was to compare myocardial mechanics of constrictive pericarditis (CP) with restrictive cardiomyopathy (RCM), or healthy controls; to assess the impact of pericardial thickening detected by cardiac magnetic resonance on regional myocardial mechanics in CP; and to quantitate the effect of pericardiectomy on myocardial mechanics in CP.Myocardial mechanics were evaluated by 2-dimensional speckle tracking in 52 consecutive patients with CP who underwent cardiac magnetic resonance examination before pericardiectomy, 35 patients with RCM, and 26 control subjects. CP patients had selectively depressed left ventricular (LV) anterolateral wall strain (LWS) and right ventricular (RV) free wall longitudinal systolic strain (FWS) but preserved LV septal wall systolic strain (SWS). In a comparison of RCM and normals, CP patients had significantly lower regional longitudinal systolic strain ratios (CP versus RCM and normal; LVLWS/LVSWS: 0.8±0.2 versus 1.1±0.2 and 1.0±0.2; P<0.001, RVFWS/LVSWS: 0.8±0.4 vs. 1.4±0.5 and 1.2±0.2; P<0.001). LVLWS/LVSWS was more robust than the LV lateral wall to LV septal wall ratio of early diastolic velocities at the LV base (LE′/SE′) in differentiating CP from RCM (area under the curve=0.91 versus 0.76; P=0.011). There was a significant inverse correlation between pericardial thickness and respective ventricular strains (P=0.001). Pericardiectomy resulted in the improvement of the depressed LVLWS/LVSWS (0.83±0.18-0.95±0.12; P<0.001).Regional longitudinal systolic strain ratios are robust novel diagnostic tools for CP. Regional myocardial mechanics inversely correlates with adjacent pericardial segment thickness detected by cardiac magnetic resonance, and pericardiectomy leads to systolic strain improvement, which is more pronounced in right ventricular and LV free walls. [ABSTRACT FROM AUTHOR]

The role of exercise-induced pulmonary hypertension in decision making regarding surgical timing for asymptomatic chronic mitral regurgitation is controversial. We reasoned that the exercise-induced pulmonary hypertension response could not be interpreted without knowledge of right ventricular (RV) function. The aim of this study was to assess the role of RV measures at rest and during exercise as predictors of prognosis in asymptomatic mitral regurgitation.Comprehensive resting and exercise echocardiography was performed in 196 consecutive patients (56±13 years; 64% male) with isolated moderate to severe mitral regurgitation (effective regurgitant orifice area, 38±18 mm2) and preserved left ventricular function in whom initial management was expectant. Left ventricular and RV longitudinal strain were analyzed at rest using velocity vector imaging. Tricuspid annular plane systolic excursion and systolic pulmonary arterial pressure were measured at rest and during exercise. Valve surgery was performed in 88 patients (45%) over 27±15 months. After adjustment for age and sex in a Cox proportional-hazards model, exercise tricuspid annular plane systolic excursion (hazard ratio, 0.26; P<0.001), was associated with valve surgery-free survival, independent of resting left ventricular strain (hazard ratio, 1.09; P=0.027), exercise systolic pulmonary arterial pressure (hazard ratio, 1.03; P<0.001), and resting RV strain (hazard ratio, 1.10; P=0.004). In sequential Cox models, a model based on clinical data and left ventricular strain (χ2, 15.9) was improved by RV strain and RV chamber size (χ2, 28.8; P=0.003) and exercise systolic pulmonary arterial pressure (χ2, 40.1; P=0.002) and further increased by exercise tricuspid annular plane systolic excursion (χ2, 52.2; P=0.002).Exercise-induced RV dysfunction provides important incremental prognostic value in the management of asymptomatic mitral regurgitation. [ABSTRACT FROM AUTHOR]

The article presents a study on the relationship between serial measurements of functional mitral regurgitation (MR) and reverse remodeling and the outcomes in cardiac resynchronization therapy (CRT) patients. The researchers observed patients who underwent CRT device implantation at Cleveland Clinic in Ohio from January 2003 to June 2006. They found that early MR reduction seems to be associated with a greater potential decrease in left ventricular end-systolic volume index change (LVESVi).

It is unknown whether longitudinal rotation (LR), often seen in cardiac resynchronization therapy candidates, may affect mitral annular early diastolic (E′) velocities and tricuspid annular motion. We assessed whether (1) LR affects the amplitude and timing of septal and lateral mitral annular E′ velocities and tricuspid annular systolic and E′ velocities and (2) if systolic strain heterogeneity seen in cardiac resynchronization therapy patients with LR extends into diastole.Ninety-nine cardiac resynchronization therapy candidates with suitable baseline echocardiograms were identified. Early diastolic (E′) and systolic myocardial velocities of the tricuspid annulus and E′ velocities of the septal and lateral part of the mitral annulus were analyzed from tissue Doppler images. Longitudinal rotation and basal systolic and diastolic strain rates were analyzed by speckle-tracking. LR correlated with lateral mitral annular E′ (r=0.45, P<0.001), tricuspid annular E′ (r=-0.3, P=0.003), and with a difference between septal and lateral mitral annular E′ velocities (r=-0.49, P<0.001) but not with septal mitral annular E′ velocity. LR also correlated with tricuspid annular systolic velocity (r=0.60, P<0.001). After categorizing the patients according to the quartiles of their LR, we showed that with decreasing quartile number, heterogeneity of systolic (P=0.003) but not diastolic (P>0.1) strain rates increased.LR direction and magnitude correlates with the amplitude of, and relative differences between, diastolic velocities of tricuspid, lateral mitral, and septal mitral annulus, which are a cornerstone of diastolic function assessment. LR is associated with systolic but not with diastolic regional heterogeneity. [ABSTRACT FROM AUTHOR]

The article presents a study which aimed to find out if a new echocardiographic technique, the two-dimensional (2D) strain imaging, is better at tracking treatment of acute decompensated heart failure (ADHF) patients than the use of conventional echocardiographic methods such as the right ventricular fractional area change (RVAC). The study concluded that the use of 2D strain imaging in monitoring intensive medical therapy of patients with ADHF contributed to lower long-term adverse events.

The article presents a study that investigates the impact of enhancing vagal tone acquired from chronic vagus nerve stimulation (VNS) on heart failure development in a canine high-rate ventricular pacing model in dogs. Study shows an improvement on heart rate variability and baroreflex sensitivity in the VNS dogs. Results are said to have indicated that chronic VNS can improve cardiac autonomic control and that VNS is associated with pronounced anti-inflammatory effects.

Background: The severity classification of functional mitral regurgitation (FMR) remains controversial despite adverse prognosis and rapidly evolving interventions. Furthermore, it is unclear if quantitative assessment with cardiac magnetic resonance can provide incremental risk stratification for patients with ischemic cardiomyopathy (ICM) or non-ICM (NICM) in terms of FMR and late gadolinium enhancement (LGE). We evaluated the impact of quantitative cardiac magnetic resonance parameters on event-free survival separately for ICM and NICM, to assess prognostic FMR thresholds and interactions with LGE quantification., Methods: Patients (n=1414) undergoing cardiac magnetic resonance for cardiomyopathy (ejection fraction<50%) assessment from April 1, 2001 to December 31, 2017 were evaluated. The primary end point was all-cause death, heart transplant, or left ventricular assist device implantation during follow-up. Multivariable Cox analyses were conducted to determine the impact of FMR, LGE, and their interactions with event-free survival., Results: There were 510 primary end points, 395/782 (50.5%) in ICM and 114/632 (18.0%) in NICM. Mitral regurgitation-fraction per 5% increase was independently associated with the primary end point, hazards ratios (95% CIs) of 1.04 (1.01-1.07; P =0.034) in ICM and 1.09 (1.02-1.16; P =0.011) in NICM. Optimal mitral regurgitation-fraction threshold for moderate and severe FMR were ≥20% and ≥35%, respectively, in both ICM and NICM, based on the prediction of the primary outcome. Similarly, optimal LGE thresholds were ≥5% in ICM and ≥2% in NICM. Mitral regurgitation-fraction×LGE emerged as a significant interaction for the primary end point in ICM ( P =0.006), but not in NICM ( P =0.971)., Conclusions: Mitral regurgitation-fraction and LGE are key quantitative cardiac magnetic resonance biomarkers with differential associations with adverse outcomes in ICM and NICM. Optimal prognostic thresholds may provide important clinical risk prognostication and may further facilitate the ability to derive selection criteria to guide therapeutic decision-making., Competing Interests: Disclosures None.

Background: Antibodies to the beta1-adrenergic receptor (beta1AR) are detected in a substantial number of patients with idiopathic dilated cardiomyopathy (DCM). The mechanism whereby these autoantibodies exert their pathogenic effect is unknown. Here, we define a causal mechanism whereby beta1AR-specific autoantibodies mediate noninflammatory cardiomyocyte cell death during murine DCM., Methods and Results: We used the beta1AR protein as an immunogen in SWXJ mice and generated a polyclonal battery of autoantibodies that showed selective binding to the beta1AR. After transfer into naive male hosts, beta1AR antibodies elicited fulminant DCM at high frequency. DCM was attenuated after immunoadsorption of beta1AR IgG before transfer and by selective pharmacological antagonism of host beta1AR but not beta2AR. We found that beta1AR autoantibodies shifted the beta1AR into the agonist-coupled high-affinity state and activated the canonical cAMP-dependent protein kinase A signaling pathway in cardiomyocytes. These events led to functional alterations in intracellular calcium handling and contractile function. Sustained agonism by beta1AR autoantibodies elicited caspase-3 activation, cardiomyocyte apoptosis, and DCM in vivo, and these processes were prevented by in vivo treatment with the pan-caspase inhibitor Z-VAD-FMK., Conclusions: Our data show how beta1AR-specific autoantibodies elicit DCM by agonistically inducing cardiomyocyte apoptosis.

We have reported that the Myocor Coapsys (Myocor, Inc, Maple Grove, MN) device treated functional mitral regurgitation (MR) by reducing mitral annular dimension and repositioning papillary muscles. This study was conducted to evaluate the optimal Coapsys device sizing level. The Coapsys device was implanted in seven dogs after induction of MR by rapid ventricular pacing. The device consists of anterior and posterior pads connected by a subvalvular cord. The device was tightened in 5% increments of the left ventricular epicardial to epicardial dimension up to 40%. Hemodynamic and echocardiographic measurements were repeated at each tightening level. The Coapsys significantly reduced or eliminated functional MR, and the reduction was maximized at the 30% tightening level or lower in all cases. Although the left ventricular end diastolic volume decreased significantly, forward stroke volume was maintained until the 35% tightening level. The forward ejection fraction significantly increased from 33 +/- 24% at baseline to 62 +/- 42% at 40% tightening level. Mean aortic pressure decreased slightly but significantly. The Coapsys device can be applied over a broad range of tightening levels with significant reduction in MR without negative physiologic impact. This feature makes the device usable [corrected] in a variety of clinical settings.