Conduit Flow Compensates for Impaired Left Atrial Passive and Booster Functions in Advanced Diastolic Dysfunction.

BACKGROUND: Quantification of left atrial (LA) conduit function and its contribution to left ventricular (LV) filling is challenging because it requires simultaneous measurements of both LA and LV volumes. The functional relationship between LA conduit function and the severity of diastolic dysfunction remains controversial. We studied the role of LA conduit function in maintaining LV filling in advanced diastolic dysfunction. METHODS: We performed volumetric and flow analyses of LA function across the spectrum of LV diastolic dysfunction, derived from a set of consecutive patients undergoing multiphasic cardiac computed tomography scanning (n=489). From LA and LV time-volume curves, we calculated 3 volumetric components: (1) early passive emptying volume; (2) late active (booster) volume; and (3) conduit volume. Results were prospectively validated on a group of patients with severe aortic stenosis (n=110). RESULTS: The early passive filling progressively decreased with worsening diastolic function (P<0.001). The atrial booster contribution to stroke volume modestly increases with impaired relaxation (P=0.021) and declines with more advanced diastolic function (P<0.001), thus failing to compensate for the reduction in early filling. The conduit volume increased progressively (P<0.001), accounting for 75% of stroke volume (interquartile range, 63-81%) with a restrictive filling pattern, compensating for the reduction in both early and booster functions. Similar results were obtained in patients with severe aortic stenosis. The pulmonary artery systolic pressure increased in a near-linear fashion when the conduit contribution to stroke volume increased above 60%. Maximal conduit flow rate strongly correlated with mitral E-wave velocity (r=0.71; P<0.0001), indicating that the increase in mitral E wave in diastolic dysfunction represents the increased conduit flow. CONCLUSIONS: An increase in conduit volume contribution to stroke volume represents a compensatory mechanism to maintain LV filling in advanced diastolic dysfunction. The increase in conduit volume despite increasing LV diastolic pressures is accomplished by an increase in pulmonary venous pressure.

Ser194Leu DSG2 mutation, associated with arrhythmogenic left ventricular cardiomyopathy and ventricular tachycardia.

INTRODUCTION: Arrhythmogenic cardiomyopathy (AC) is an inherited cardiomyopathy characterized by fibro-fatty replacement of cardiomyocytes, leading to life-threatening ventricular arrhythmia and heart failure. Pathogenic variants of desmoglein2 gene (DSG2) have been reported as genetic etiologies of AC. In contrast, many reported DSG2 variants are benign or variants of uncertain significance. Correct genetic variant classification is crucial for determining the best medical therapy for the patient and family members. METHODS: Pathogenicity of the DSG2 Ser194Leu variant that was identified by whole exome sequencing in a patient, who presented with ventricular tachycardia and was diagnosed with AC, was investigated by electron microscopy and immunohistochemical staining of endomyocardial biopsy sample. RESULTS: Electron microscopy demonstrated a widened gap in the adhering junction and a less well-organized intercalated disk region in the mutated cardiomyocytes compared to the control. Immunohistochemical staining in the proband diagnosed with AC showed reduced expression of desmoglein 2 and connexin 43 and intercalated disc distortion. Reduced expression of DSG2 and Connexin 43 were observed in cellular cytoplasm and gap junctions. Additionally, we detected perinuclear accumulation of DSG2 and Connexin 43 in the proband sample. CONCLUSION: Ser194Leu is a missense pathogenic mutation of DSG2 gene associated with arrhythmogenic left ventricular cardiomyopathy.

Comparison Between Echocardiography and Cardiac Computed Tomography in the Evaluation of Diastolic Dysfunction and Prediction of Heart Failure.

Recent data indicate that left atrial (LA) function assessment by cardiac computed tomography (CT) is closely related to diastolic dysfunction (DD). Therefore, we aimed to perform a direct comparison between CT and echocardiography for diagnosis of advanced DD and prediction of future heart failure or cardiovascular death. We identified 340 patients who had both spiral cardiac CT and a proximate echocardiogram. LA total emptying fraction (LATEF), a measure of global LA function, was automatically calculated from CT data, as a surrogate for diastolic function and was compared with echocardiographic grades of diastolic function. The area under the receiver operating characteristic curve for LATEF to differentiate between advanced DD (grades 2 and 3) and all other grades was 0.84 (0.79 to 0.88). Over a median of 4 years, 69 events (admissions for heart failure and cardiovascular deaths) occurred. By multivariate Cox analysis, LATEF <40% provided incremental prognostic information after adjustments for advanced DD by echocardiography (hazard ratio 2.15, 95% confidence interval 1.13 to 3.94). There was a significant interaction (p = 0.03) between LATEF and echocardiography-based diastolic grades. Stratified analyses within the diastolic function groups revealed that LATEF <40% was equivalent to echocardiography in predicting events in the subgroup with advanced DD by echocardiography (p = 0.20) but was associated with a significantly higher event rates in patients with normal filling pressures (p = 0.0001) or indeterminate diastolic function (p = 0.04) by echocardiography. In conclusion, LA function derived from CT can accurately detect advanced DD diagnosed by echocardiography and has additive value to echocardiography-derived DD.

Left atrial function by cardiac computed tomography is a predictor of heart failure and cardiovascular death.

OBJECTIVES: We sought to evaluate cardiac CT angiography (CCTA)-based assessment of left atrial (LA) function as a predictor of hospitalizations for heart failure (HF) and cardiovascular (CV) mortality. METHODS: LA function was evaluated using automatic derivation of LA volumes to calculate LA total emptying fraction (LATEF) in 788 consecutive patients with normal sinus rhythm who had undergone spiral CT scans. The relationship between LATEF evaluated by CCTA and the composite endpoint of admission for HF or CV mortality was analyzed using Cox models. RESULTS: During a median follow-up of 4 years, there were 100 events, 62 HF hospitalizations, and 38 cardiovascular deaths. Mean LATEF was 30.7 ± 10.7% and 40.5 ± 11.2% in patients with and without events, respectively (p < 0.0001). A high LATEF (upper tertile > 46%) was associated with a very low event rate (3.5% at 6 years [95% CI 1.7-7.1%]). The adjusted HR for HF or CV mortality was 4.37 (95% CI 1.99-9.60) in the lowest LATEF tertile, and 2.29 (95% CI 1.03-5.14) in the middle tertile, relative to the highest tertile. For the endpoint of HF alone, adjusted HR for the lowest LATEF tertile was 5.93 (95% CI 2.23-15.82) and for the middle tertile 2.89 (95% CI 1.06-7.86). The association of LATEF with outcome was similar for patients with both reduced and preserved left ventricular (LV) ejection fraction (Pinteraction = 0.724). Reduced LATEF was associated with a high event rate, even when coupled with normal LA volume. CONCLUSION: CCTA-derived LA function is a predictor of HF hospitalization or CV death, independent of clinical risk factors, LA volume, and LV systolic function. KEY POINTS: • Left atrial function can be automatically derived from cardiac CTA scans. • Cardiac CTA-derived left atrial function is a predictor of hospitalization for heart failure and cardiovascular death. • Evaluation of left atrial function could be useful in identifying patients at risk of heart failure.

Increased Rate of New-onset Left Bundle Branch Block in Patients With Bicuspid Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation (From a National Registry).

There is a growing interest in transcutaneous aortic valve implantation (TAVI) therapy among patients with bicuspid severe aortic stenosis (BAV). Conduction disturbances remain a frequent complication of TAVI, and new-onset permanent LBBB (NOP-LBBB) post-TAVI may be a marker of worse outcomes. We aimed to evaluate the rate of NOP-LBBB following TAVI among patients with BAV as compared to tricuspid severe aortic stenosis (TAV). Patients enrolled in the multicenter (5 centers) Bicuspid AS TAVI Registry were reviewed and compared with patients with TAV. Patients with previous aortic valve replacement, other valve morphologies and those with preprocedural LBBB or pacemaker were excluded. NOP-LBBB was defined as LBBB first detected and persisting 30-days following TAVI. A total of 387 patients (66 with BAV, 321 with TAV), age 80.3 ± 7.3, 47% females were analyzed. The device success rates were 95% in both groups without any conversions to surgery. The rate of NOP-LBBB was significantly higher among patients with BAV versus TAV (29.2% vs 16.9%, p = 0.02). However, the rate of post procedural pacemaker implantation was similar (14.8% vs 12.5%; respectively, p = 0.62). In BAV and TAV groups, 1-year mortality (6.1% vs 7.2%; respectively, p = 0.75) and stroke rates (6.1% vs 3.5%; respectively, p = 0.30) were not significantly different. Multivariate analysis identified BAV as an independent predictor of NOP-LBBB (AdjOR = 2.7, 95%CI 1.3 to 5.4). Furthermore, BAV subtypes with raphe (type 1) were identified as independent predictors of NOP-LBBB (AdjOR = 3.2, 95%CI: 1.5 to 6.7). In conclusion, patients with BAV undergoing TAVI have greater risk for developing NOP-LBBB compared with patients with TAV and the presence of raphe was associated with increased risk of NOP-LBBB. The prognostic significance for this finding warrants further evaluation in future studies.

Accuracy of Diastolic Function by Cardiac Computed Tomography Relative to Echo-Doppler: Additive Clinical and Prognostic Value.

OBJECTIVES: We aimed to assess the agreement between cardiac computed tomography (CT) and echo for diagnosing advanced diastolic dysfunction (DD) and to assess the prognostic value of CT-based parameters. METHODS: One hundred one consecutive patients who had both CT and echo-Doppler within 1 month were included. Diastolic function was assessed by CT using a previously validated method, based on left atrial volume changes, and compared with echocardiography grades 0 to 3. Patients were followed up for a combined outcome of cardiac death and hospitalization for heart failure. RESULTS: By operating characteristic curve analysis, the best CT-based parameter for predicting advanced DD based on echo was left atrial total emptying fraction. Left atrial total emptying fraction <36% had sensitivity/specificity of 76%/86%. Agreement between echo and CT for detecting advanced (grades 2/3) DD was substantial (κ = 0.62, P < 0.0001). By Cox multivariate analysis, left atrial total emptying fraction was a powerful independent predictor of outcome at 3 years (hazard ratio, 8.0 [2.2-28.4]; P < 0.0001). CONCLUSIONS: Computed tomography-based assessment of DD has a good agreement with echo-Doppler-based results. Left atrial total emptying fraction seems to have a strong prognostic value.

Short membranous septum length in bicuspid aortic valve stenosis increases the risk of conduction disturbances.

BACKGROUND: Distinct anatomical features predispose bicuspid AS patients to conduction disturbances after TAVR. This study sought to evaluate whether the incidence of permanent pacemaker implantation (PPMI) and left bundle branch block (LBBB) in patients with bicuspid aortic stenosis (AS) following transcatheter aortic valve replacement (TAVR) is related to an anatomical association between bicuspid AS and short membranous septal (MS) length. METHODS: Sixty-seven consecutive patients with bicuspid AS from a Bicuspid AS TAVR multicenter registry and 67 propensity-matched patients with tricuspid AS underwent computed tomography before TAVR. RESULTS: MS length was significantly shorter in bicuspid AS compared with tricuspid AS (6.2 ± 2.5 mm vs. 8.4 ± 2.7 mm, respectively; p < 0.001). In patients with bicuspid AS, MS length and aortic valve calcification were the most powerful pre-procedural independent predictors of PPMI or LBBB (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.15 to 1.55, p = 0.003 and OR: 1.92, 95% CI: 1.1 to 3.34, p = 0.022, respectively). When taking into account pre- and post-procedural parameters, aortic valve calcification and the difference between MS length and implantation depth were the most powerful independent predictors of PPMI or LBBB in patients with bicuspid AS (OR: 1.82, 95%: 1.1 to 3.1, p = 0.027; OR: 1.25, 95% CI: 1.10 to 1.38, p = 0.003). CONCLUSION: MS length, which was significantly shorter in bicuspid AS compared with tricuspid AS, aortic valve calcification, and device implantation deeper than MS length predict PPMI or LBBB in bicuspid AS after TAVR.

Risk Factors for the Development of Functional Tricuspid Regurgitation and Their Population-Attributable Fractions.

OBJECTIVES: The objective of this study was to determine risk factors for progression to hemodynamically significant tricuspid regurgitation (TR) and the population burden attributable to these risk factors. BACKGROUND: Few data are available with regard to risk factors associated with the development of hemodynamically significant functional TR. METHODS: A total of 1,552 subjects were studied beginning with an index echocardiogram demonstrating trivial or mild TR. Risk factors for progression to moderate or severe TR were determined by using logistic regression and classification trees. Population attributable fractions were calculated for each risk factor. RESULTS: During a median follow-up time of 38 (interquartile range [IQR]: 26 to 63) months, 292 patients (18.8%) developed moderate/severe TR. Independent predictors of TR progression were age, female sex, heart failure, pacemaker electrode, atrial fibrillation (AF), and indicators of left heart disease, including left atrial (LA) enlargement, elevated pulmonary artery pressure (PAP), and left-sided valvular disease. Classification and regression tree analysis demonstrated that the strongest predictors of TR progression were PAP of ≥36 mm Hg, LA enlargement, age ≥60 years, and AF. In the absence of these 4 risk factors, progression to moderate or severe TR occurred in ∼3% of patients. Age (28.4%) and PAP (20.5%) carried the highest population-attributable fractions for TR progression. In patients with TR progression, there was a marked concomitant increase of incident cases of elevated PAP (40%); mitral and aortic valve intervention (12%); reductions in left ventricular ejection fraction (19%), and new AF (32%) (all p < 0.01). CONCLUSIONS: TR progression is determined mainly by markers of increased left-sided filling pressures (PAP and LA enlargement), AF, and age. At the population level, age and PAP are the most important contributors to the burden of significant TR. TR progression entails a marked parallel increase in the severity of left-sided heart disease.

Automated 4-dimensional regional myocardial strain evaluation using cardiac computed tomography.

Evaluation of myocardial regional function is generally performed by visual "eyeballing" which is highly subjective. A robust quantifiable parameter of regional function is required to provide an objective, repeatable and comparable measure of myocardial performance. We aimed to evaluate the clinical utility of novel regional myocardial strain software from cardiac computed tomography (CT) datasets. 93 consecutive patients who had undergone retrospectively gated cardiac CT were evaluated by the software, which utilizes a finite element based tracking algorithm through the cardiac cycle. Circumferential (CS), longitudinal (LS) and radial (RS) strains were calculated for each of 16 myocardial segments and compared to a visual assessment, carried out by an experienced cardiologist on cine movies of standard "echo" views derived from the CT data. A subset of 37 cases was compared to speckle strain by echocardiography. The automated software performed successfully in 93/106 cases, with minimal human interaction. Peak CS, LS and RS all differentiated well between normal, hypokinetic and akinetic segments. Peak strains for akinetic segments were generally post-systolic, peaking at 50 ± 17% of the RR interval compared to 43 ± 9% for normokinetic segments. Using ROC analysis to test the ability to differentiate between normal and abnormal segments, the area under the curve was 0.84 ± 0.01 for CS, 0.80 ± 0.02 for RS and 0.68 ± 0.02 for LS. There was a moderate agreement with speckle strain. Automated 4D regional strain analysis of CT datasets shows a good correspondence to visual analysis and successfully differentiates between normal and abnormal segments, thus providing an objective quantifiable map of myocardial regional function.

Lack of Increased Cardiovascular Risk due to Functional Tricuspid Regurgitation in Patients with Left-Sided Heart Disease.

BACKGROUND: Significant tricuspid regurgitation (TR) is associated with higher risk for adverse cardiovascular outcomes. Left-sided heart disease (LHD) is a potentially important confounder of this association because it is strongly linked to both TR and clinical outcome. METHODS: We studied 5,886 patients who were followed for a period of 10 years after the index echocardiographic examination. The relationship between TR severity and the end point of admission for heart failure or cardiovascular mortality was analyzed using competing risk analysis, Cox model, and propensity score matching. RESULTS: Higher TR grade was associated with markers of LHD including left ventricular systolic dysfunction, valvular heart disease ≥ moderate, left atrial enlargement, and pulmonary hypertension (all P < .001). There was a significant interaction between TR and the presence of LHD with regard to the end point of heart failure in the competing risks model (P = .01) and the combined end point of heart failure and cardiovascular mortality (P = .02). In both models, moderate/severe TR was associated with higher risk for heart failure (hazard ratio [HR] = 3.10; 95% CI, 1.41-6.84; P = .005) and the combined end point of heart failure or cardiovascular mortality (HR = 2.75; 95% CI, 1.33-5.63, P = .006) only in patients without LHD. Propensity score matching yielded 350 patient pairs, of which 88% had LHD. The HR for heart failure or cardiovascular mortality at 10 years was 0.78 (95% CI, 0.56-1.08; P = .14) in the moderate/severe TR group as compared with the trivial/mild TR. CONCLUSIONS: Moderate or severe functional TR portends an increased risk for heart failure and cardiovascular mortality only when isolated, without concomitant LHD.

Tricuspid regurgitation in acute heart failure: is there any incremental risk?

Aim: Significant tricuspid regurgitation (TR) is common in heart failure (HF) and portends poor prognosis. We sought to determine whether the poor outcome results from the TR itself, or whether the TR is a surrogate marker of advanced left-sided myocardial or valvular heart disease. Methods and results: We studied 639 patients admitted for acute HF. The relationship between TR severity and the endpoint of readmission for HF or mortality was assessed after adjustment for multiple clinical and echocardiographic parameters. Higher TR grade was associated with higher congestion score and with other cardiac abnormalities including reduced left ventricular systolic function, moderate or severe mitral regurgitation, pulmonary hypertension (PH, defined as pulmonary artery systolic pressure ≥ 50 mmHg), and right ventricular dysfunction (all P < 0.001). Only 7% of patients with moderate or severe TR were free of other cardiac lesions. In adjusted models, moderate or severe TR was not associated with readmission for HF or mortality [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 0.97-1.57]. Patients with moderate/severe TR had similar risk for HF readmission or death compared with patients with trivial/mild TR when PH was not present (HR 1.17; 95% CI 0.78-1.75, P = 0.40) whereas the risk was higher in moderate/severe TR and PH (HR 1.78; 95% CI 1.34-2.36, P < 0.0001). Conclusion: Patients presenting with symptomatic HF and significant TR have multiple coexisting cardiac abnormalities. TR provides no additive risk in the presence of normal or mildly elevated pulmonary pressures. However, it is associated with excess rehospitalizations and mortality in patients with PH.

Assessment of mitral regurgitation by 3-dimensional proximal flow convergence using magnetic resonance imaging: comparison with echo-Doppler.

To test the feasibility of assessing mitral regurgitation (MR) severity using cardiac magnetic resonance (CMR) 4D velocity vectors to quantify regurgitant volume (RVol) by analysis of the proximal flow convergence, compared to Doppler based proximal isovelocity surface area (PISA) and CMR volume-based methods. In a prospectively designed study, 27 patients with various grades of MR underwent CMR and echo-Doppler on the same day. By CMR, multiple slices were obtained parallel to the mitral valve by phase-contrast imaging, using 3D velocity vectors, as well as short-axis cine images for left and right ventricular volume measurements. Using dedicated software developed in our laboratory, the perimeter of the proximal flow convergence region was semi-automatically measured for each temporal phase, and for each short-axis slice. The CMR-PISA RVol was calculated as the sum of PISA perimeters throughout systole, multiplied by slice width. For comparison, CMR-volumetric RVol was calculated by 2 methods: Volumetric (difference between left and right ventricular stroke volumes) and Flow-based (stroke volume -aortic flow). Echo-PISA RVol was calculated by echo-Doppler based PISA method. RVol by CMR-PISA correlated highly with echo-PISA (r = 0.87) and with CMR-volumetric (r = 0.86) and CMR-flow (r = 0.72). For comparison Doppler-RVol and CMR-volume-based RVol had r = 0.83. On average CMR-PISA was 16 ± 25 ml less than echo-PISA, but 12 ± 22 ml larger than CMR-volumetric RVol. The observed 3D shape of the PISA envelope by 4D-CMR resembled a hemiellipsoid rather than a hemisphere. This feasibility study suggests that CMR-based 4D-PISA may be able to assess MR severity quantitatively without any geometric assumptions.

[CARDIAC MAGNETIC RESONANCE AS A TOOL FOR RAPID DIAGNOSIS OF EOSINOPHILIC MYOCARDITIS].

INTRODUCTION: Eosinophilic myocarditis is a rare disease with an unknown etiology, that may be severe and even lethal. Early treatment based on steroids may prevent deterioration and even lead to complete cure, but it requires rapid diagnosis. The gold standard for diagnosis of the disease is by endomyocardial biopsy but this test has low sensitivity and involves risks to the patient. This case report presents a patient who was admitted with complaints of chest pain. During her workup, with the help of cardiac MRI, eosinophilic myocarditis with mild deterioration in heart function was diagnosed. Treatment with prednisone resulted in rapid improvement in patient complaints, laboratory indices and heart function.

Automatic Estimation of Optimal Deployment of Transcatheter Aortic Valve Implantation Using Computed Tomography.

BACKGROUND: A comparison was made between the accuracy of and time saved by using novel automated software for pre-procedural computed tomography (CT) planning before transcatheter aortic valve implantation (TAVI) and manual methods. Preprocedural CT to assess aortic annulus dimensions and predict the optimal C-arm implant angle before TAVI can reduce complications related to incorrect prosthesis sizing and positioning. METHODS: A total of 61 consecutive patients underwent TAVI using either the SAPIEN XT or CoreValve prosthesis. Pre-procedural CT scans were analysed using three methods: automatic; semi-automatic; and manual. For each method, annular dimensions were measured and the optimal implantation angle was predicted. After TAVI the actual post-deployment angle orthogonal to the prosthesis was determined using aortic fluoroscopy. The difference between the predicted angle by CT and the measured post-deployment angle was calculated for each method. RESULTS: For all methods the mean angular difference with the actual post-deployment angle was similar at ~9 ± 7°. There was a significant difference between the SAPIEN XT (6.6 ± 5.8°) and CoreValve (11.5 ± 6.9°, p <0.001) prostheses due to a consistently greater left anterior oblique and caudal angulation for the CoreValve. Although the annular area correlated well among all methods, 'automatic' results were consistently larger than 'manual' results. Interobserver variability was low for all measures. The fully automatic method saved 98 s, and the semiautomatic method 40 s per case. CONCLUSIONS: The use of automatic software enabled a rapid and accurate prediction of implantation angles, though results differed for specific manufacturers. Annular areas were overestimated by the automatic method, and thus required manual adjustments.

Assessment of Diastolic Function in Hypertrophic Cardiomyopathy by Computed Tomography-Derived Analysis of Left Ventricular Filling.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is characterized by diastolic dysfunction, which is difficult to assess by noninvasive methods. We hypothesized that measurement of simultaneous left ventricular (LV) and left atrial (LA) volume changes by cardiac computed tomography would be useful in the assessment of diastolic function in HCM. METHODS: We studied 21 patients with HCM and 21 age-matched controls. The LA and LV volumes were calculated and early and late diastolic volume changes derived. RESULTS: The HCM patients had significantly larger LA volumes and reduced LA total emptying fraction (30 ± 7% vs 42 ± 6%; P < 0.0001). Conduit volume was increased (30 ± 6 vs 22 ± 4 mL/m; P < 0.0001) and contributed a significantly higher proportion of total LV diastolic filling, suggesting that passive filling of the LV compensates for LA dysfunction, but at the expense of increased pulmonary filling pressure. CONCLUSIONS: This study suggests that simultaneous depiction of computed tomography-derived LV and LA volume changes can characterize diastolic dysfunction in HCM.