Left Atrial Area Research Articles

Multiparametric cardiac magnetic resonance assessmenti in sickle-beta-thalassemia

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The MIOT project receives “no-profit support” from industrial sponsorships (Chiesi Farmaceutici S.p.A., ApoPharma Inc.). Background. Sickle β-thalassemia (Sβ-thal) is a hereditary hemoglobinopathy resulting from the combined heterozygosity for sickle cell and β-thalassemia genes. Cardiac involvement in Sβ-thal patients has been poorly investigated. Aim. We aimed to evaluate myocardial iron overload and cardiac function by cardiovascular magnetic resonance (CMR) in patients with Sβ-thal. Methods. One hundred and eleven Sβ-thal patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network were studied and compared with 46 sickle cell disease (SCD) patients. Biatrial and biventricular function CMR parameters of Sβ-thal patients were compared with those of 111 healthy volunteers, matched by gender and age. Myocardial iron overload (MIO) was assessed by T2* technique. Cine images were acquired to quantify biventricular function. Macroscopic myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) technique. Results. In Sβ-thal and SCD patients morphological and functional MR parameters were not significantly different, except for left atrial area and SVI (p = 0.023 and p = 0.048, respectively) that were significantly higher in SCD patients. No significant differences between the two groups were found in terms of myocardial iron overload and macroscopic myocardial fibrosis. When compared to healthy subjects, Sβ-thal patients showed significantly higher bi-atrial and biventricular parameters except for LVEF that was significantly lower (Fig.1). Conclusions. The CMR analysis confirmed that Sβ-thal and SCD patients are phenotypically similar. Since Sβ-thal patients showed markedly different morphological and functional indices from healthy subjects, it would be useful to identify Sβ-thal/SCD-specific bi-atrial and biventricular reference values.

Left atrial strain analysis in hypertensive heart disease and hypertrophic cardiomyopathy by cardiovascular magnetic resonance feature tracking

Abstract Funding Acknowledgements Type of funding sources: None. Background Increasing evidence suggests that left atrial (LA) deformation is a sensitive marker of diastolic dysfunction in hypertrophic phenotypes. However, there is little data about the impact of hypertension on LA function; furthermore, LA deformation in hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) has not been compared yet. Purpose The aim of this study is to compare atrial dimensions and function, evaluated by cardiovascular magnetic resonance feature tracking (CMR-FT) in patients with HHD, HCM and healthy subjects (HS). Methods 67 patients (20 HHD, 27 HCM, 20 HS) underwent CMR and were included in the study. Patients were matched for age, sex and BSA; HHD and HCM were also comparable for LV mass index and ejection fraction (EF). CMR-FT atrial strain analysis was performed using Qstrain, Medis software to obtain i) LA conduit function, ii) LA booster pump function), iii) LA reservoir function, iv) LA volumes and EF. Tissue Doppler echocardiography was used to assess diastolic function, including E/e’. LA stiffness was calculated as the ratio between E/e’ and LA reservoir. Both focal and interstitial myocardial fibrosis were assessed with LGE and extracellular volume (ECV) quantification. Results HHD and HCM showed impaired LA reservoir, conduit function and higher LA volumes vs HS (reservoir: 28 ± 11% and 28 ± 13% vs 41 ± 17%; conduit: 13 ± 7% and 13 ± 7% vs 22 ± 11%; LAESV: 76 ± 21 and 87 ± 22 vs 57 ± 19 ml respectively; all p ≤ 0.03). HHD and HCM were comparable for bi-ventricular morpho-functional parameters and ECV. HHD showed lower E/e’ values (8 ± 2 vs 16 ± 7, p = 0.002) and LA stiffness (0.23 ± 0.3 vs 0.74 ± 0.6, p 0.03), LA dimensions (LA area 13 ± 3 vs 16 ± 3 cm2/m2, p = 0.02 , LAESVi 41 ± 12 vs 48 ± 11 ml/m2, p = 0.05) and LGE extent (1 ± 2% vs 5 ± 5%, p = 0.001) as compared to HCM. Interestingly, HHD revealed a comparable reduced LA reservoir and conduit function (all p = 0.9) vs HCM. In HHD patients LA reservoir function was correlated with E/e’ (r -0.8, p = 0.02), but not in HCM. Conversely, LA reservoir function was correlated with LV mass index in HCM (r -0.5, p < 0.01). Conclusions HHD patients showed a similar and significant impairment of LA function, with lower LA dimensions and E/e’ compared to HCM with similar LV mass index and preserved function. CMR-FT atrial strain analysis could represent a useful tool for HHD management, able to detect diastolic dysfunction (and/or atrial dysfunction) earlier than traditional markers. Further studies are needed to explore the relationship of LA deformation to heart failure symptoms and atrial fibrillation occurrence and potential changes related to response to therapy.

IGFBP7 and GDF-15, but not P1NP, are associated with cardiac alterations and 10-year outcome in an elderly community-based study

BackgroundLittle is known about the clinical value of Insulin-like growth factor-binding protein-7 (IGFBP7), a cellular senescence marker, in an elderly general population with multiple co-morbidities and high prevalence of asymptomatic cardiovascular ventricular dysfunction. Inflammation and fibrosis are hallmarks of cardiac aging and remodelling. Therefore, we assessed the clinical performance of IGFBP7 and two other biomarkers reflecting these pathogenic pathways, the growth differentiation factor-15 (GFD-15) and amino-terminal propeptide of type I procollagen (P1NP), for their association with cardiac phenotypes and outcomes in the PREDICTOR study.Methods2001 community-dwelling subjects aged 65–84 years who had undergone centrally-read echocardiography, were selected through administrative registries. Atrial fibrillation (AF) and 4 echocardiographic patterns were assessed: E/e’ (> 8), enlarged left atrial area, left ventricular hypertrophy (LVH) and reduced midwall circumference shortening (MFS). All-cause and cardiovascular mortality and hospitalization were recorded over a median follow-up of 10.6 years.ResultsIGFBP7 and GDF-15, but not P1NP, were independently associated with prevalent AF and echocardiographic variables after adjusting for age and sex. After adjustment for clinical risk factors and cardiac patterns or NT-proBNP and hsTnT, both IGFBP7 and GDF-15 independently predicted all-cause mortality, hazard ratios 2.13[1.08–4.22] and 2.03[1.62–2.56] per unit increase of Ln-transformed markers, respectively.ConclusionsIn a community-based elderly cohort, IGFBP7 and GDF-15 appear associated to cardiac alterations as well as to 10-year risk of all-cause mortality.

Is left atrial fibrosis an independent determinant of atrial fibrillation in mitral stenosis?

We prospectively studied whether left atrial (LA) fibrosis is a determinant of atrial fibrillation (AF) in mitral stenosis in patients who underwent balloon mitral valvotomy. There were 2 groups: Group A (n = 16), with AF and Group B (n = 27), without AF. Fibrosis was assessed by MRI. Patients underwent cardioversion before MRI. There were 27 females and 16 males, aged 29 ± 6 years. The LA areas in Groups A and B were 54.3 ± 4.4 mm2 and 39.4 ± 2.3 mm2 (p < 0.05) and the LA volume index was 46.2 ± 2.9 ml/m2 vs 33 ± 3 ml/m2 respectively (p < 0.0001). The presence of LA scarring was not statistically different in the two groups.

Preoperative mitral annulus size - Can we get it right?

Objective:We looked for a correlation between the surgically measured mitral valve size and the cardiac dimensions (left ventricle internal diameter, left atrial size, aorta size, and body surface area) measured by preoperative and intraoperative echocardiography. We also assessed to see if we could predict the mitral prosthesis size based on the correlation data obtained.Methods:The hospital records of 180 patients who underwent mitral valve replacement (MVR) with TTK Chitra valve between January 2008 and December 2012 at our hospital, were studied. The correlation between surgically measured mitral annulus size to left ventricular internal diameter systolic (LVIDS) and diastolic (LVIDD), left atrial size (linear measurement), and aorta size on echocardiography and body surface area was calculated using Pearson correlation coefficient. Mean LVIDS was calculated for each valve prosthesis size separately and the correlation was studied.Results:The correlation between mitral valve prosthesis size and left ventricular internal diameter (systolic) showed a Pearson coefficient of 3.3 with significance at the level 0.01. Mitral valve size and left atrial size showed a correlation coefficient of 2.7 with significance at the level 0.01. The correlation coefficient for mitral valve size with left ventricular internal diameter diastolic, aorta and body surface area were 2.5, 1.9, and 1.8, respectively. There was a gradual increase in the mean LVIDS with increase in the prosthetic valve size. Box plot and scatter plot showed linear correlation between valve size and mean LVIDS.

Pioglitazone Inhibits Diabetes-Induced Atrial Mitochondrial Oxidative Stress and Improves Mitochondrial Biogenesis, Dynamics, and Function Through the PPAR-γ/PGC-1α Signaling Pathway.

Background: Oxidative stress contributes to adverse atrial remodeling in diabetes mellitus. This remodeling can be prevented by the PPAR-γ agonist pioglitazone via its antioxidant and anti-inflammatory effects. In this study, we examined the molecular mechanisms underlying the protective effects of pioglitazone on atrial remodeling in a rabbit model of diabetes. Methods: Rabbits were randomly divided into control, diabetic, and pioglitazone-treated diabetic groups. Echocardiographic, hemodynamic, and electrophysiological parameters were measured. Serum PPAR-γ levels, serum and tissue oxidative stress and inflammatory markers, mitochondrial morphology, reactive oxygen species (ROS) production rate, respiratory function, and mitochondrial membrane potential (MMP) levels were measured. Protein expression of the pro-fibrotic marker TGF-β1, the PPAR-γ coactivator-1α (PGC-1α), and the mitochondrial proteins (biogenesis-, fusion-, and fission-related proteins) was measured. HL-1 cells were transfected with PGC-1α small interfering RNA (siRNA) to determine the underlying mechanisms of pioglitazone improvement of mitochondrial function under oxidative stress. Results: The diabetic group demonstrated a larger left atrial diameter and fibrosis area than the controls, which were associated with a higher incidence of inducible atrial fibrillation (AF). The lower serum PPAR-γ level was associated with lower PGC-1α and higher NF-κB and TGF-β1 expression. Lower mitochondrial biogenesis (PGC-1α, NRF1, and TFAM)-, fusion (Opa1 and Mfn1)-, and fission (Drp1)-related proteins were detected. Mitochondrial swelling, higher mitochondrial ROS, lower respiratory control rate, and lower MMP were observed. The pioglitazone group showed a reversal of structural remodeling and a lower incidence of inducible AF, which were associated with higher PPAR-γ and PGC-1α. The pioglitazone group had lower NF-κB and TGF-β1 expression levels, whereas biogenesis-, fusion-, and fission-related protein expression was higher. Further, mitochondrial structure and function were improved. In HL-1 cells, PGC-1α siRNA transfection blunted the effect of pioglitazone on Mn-SOD protein expression and MMP collapse in H2O2-treated cells. Conclusion: Diabetes mellitus induces adverse atrial structural, electrophysiological remodeling, and mitochondrial damage and dysfunction. Pioglitazone prevented these abnormalities through the PPAR-γ/PGC-1α pathway.

Atrial substrate characterization in patients with atrial fibrillation and hypertrophic cardiomyopathy: Evidence for an extensive fibrotic disease

IntroductionData regarding the left atrial (LA) electroanatomical substrate in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) are missing. In this electroanatomical mapping (EAM) study, we evaluated the extent of LA fibrosis and its impact on catheter ablation outcomes in patients with HCM and AF. Materials and methodsHigh-density LA EAM was performed during AF in 28 consecutive patients with obstructive HCM and AF (42.9% displayed paroxysmal AF and 57.1% persistent AF). Propensity score (PS) matching analysis was performed to reduce the impact of potential confounding factors. PS were derived to match patients at a 1:1 ratio. Patients were matched according to age, sex and LA diameter. After PS, 28 non-HCM patients with AF were selected, and served as controls. Two different cut-off values of bipolar signal amplitude were investigated for fibrosis characterization (≤0.25 mV and ≤ 0.4 mV). HCM patients underwent pulmonary vein antral isolation (PVAI) and roof line, while non-HCM patients PVAI only. ResultsAfter the 3-month blanking period, 10 HCM patients (35.7%) displayed atrial arrhythmia recurrence. HCM patients with arrhythmia recurrence showed significantly greater low voltage areas defined as either bipolar voltage ≤0.25 mV (22.5 ± 10% vs. 5.5 ± 6.4%, p = 0.001) or ≤ 0.4 mV (32 ± 13.9% vs. 5.9 ± 5.1%, p < 0.001). The presence of low voltage areas ≤0.4 mV greater than 14.1% of the total LA area also predicted arrhythmia recurrence with excellent sensitivity (100%) and specificity (100%). Univariate analysis revealed that the extent of LA fibrosis was the only predictor of AF recurrence. After PS matching with non-HCM patients, patients with HCM exhibited wider fibrotic regions ≤0.25 mV compared to non-HCM patients (p = 0.016). ConclusionsHigh-density EAM reveals extensive LA fibrotic disease in patients with HCM, an event with certain implications in catheter ablation outcomes.

Relationship between electrocardiographic interatrial blocks and echocardiographic indices of left atrial function in acute heart failure.

The presence of an interatrial block (IAB) on surface ECG should be considered as a hallmark of atrial electrical remodelling. This is often accompanied by morphological abnormalities. We aimed to investigate the frequency of IAB and its relationship with the echocardiographic indices of left atrial (LA) remodelling in patients hospitalised with acute HF. Ninety-four consecutive HF patients underwent 12-lead ECG, transthoracic echocardiogram including a detailed study of the LA, and blood tests (including NT-proBNP) on the same day. Thirty-six patients were excluded from the analysis because of atrial fibrillation or rhythms other than sinus. Twenty-eight over 58 (48%) were males. Median age was 72 (IQR 60-82) years. The majority of patients (72%) were diagnosed as having an HF with reduced ejection fraction. Overall, 27 (46%) patients presented with an advanced III or IV NYHA functional class. Median plasma NT-proBNP was 3046 (IQR 1066-5460) pg/ml. Nearly, all the enrolled patients (90%) showed LA dilation. Nineteen patients (33%) presented with advanced IAB. There was a trend toward a more advanced age in patients with advanced IAB (median age 79 vs 68, p = 0.051). Moreover, they were more frequently treated with anticoagulants (42% vs 13%, p = 0.01), and they exhibited greater LA structural and functional remodelling documented by larger area (28 vs 26 cm2, p = 0.04) and greater minimum LA volume index-LAVi (43 ± 16 vs 36 ± 10, p = 0.04). Advanced IAB resulted to be an independent determinant of LA area (Beta 3.49 (0.37-6.60), p = 0.03) and minimum LAVi (Beta 7.22 (0.15-14.30), p = 0.045), and vice versa. LA electrical and structural remodelling is highly prevalent in a non-selected cohort of patients with acute HF. Advanced IAB on surface ECG is present in a high percentage of cases. Patients with advanced IAB tend to be older, and they exhibit higher degrees of LA structural and functional remodelling.

Pulmonary vein isolation for paroxysmal atrial fibrillation using high-power short duration radiofrequency or second-generation cryoballoon ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Differences in the left atrial (LA) tissue loss can occur following different pulmonary vein isolation (PVI) techniques. Purpose Our prospective study compared the biomarker, the LA mechanical, and the electrophysiological findings as indicators of LA myocardial damage after a high-power short duration (HPSD) with contact force radiofrequency catheter and second-generation cryoballoon (CB2) ablation of paroxysmal atrial fibrillation (AF). Methods :We enrolled 40 patients with paroxysmal AF [16 (40%) women, mean age = 55.9 ± 12.4 years] who underwent HPSD (n = 21) or CB2 (n = 19). Biomarker levels (hs-cTnT, CK-MB, hs-CRP, LDH) and the transport function of the LA by transthoracic echocardiography (TTE) were compared pre and post procedurally. High-density mapping (HDM) was performed in sinus rhythm using a multielectrode diagnostic catheter in each group to define isolated left atrial low voltage area (LVA; &amp;lt;0.2mV in bipolar voltage mapping). LA CT-angiography and HDM merge was used to calculate the post-PVI LVA and the LVA/LA surface ratio. Results Postablation hs-cTnT and hs-CRP levels were comparable in the ablation groups (HPSD: 1249 ± 469 and 9.53 ± 10.30 vs. CB2: 995 ± 280 and 12.36 ± 5.76, p = 0.065 and p = 0.732), while CK-MB and LDH levels were significantly higher following CB2 ablation (HPSD: 6.61 ± 2.62 and 349.9 ± 65.6 vs. CB2: 26.01 ± 6.88 and 451.6 ± 91.3, p &amp;lt; 0.001 and p &amp;lt; 0.001). The transport function of the LA did not change significantly by TTE after the procedure. Fractional Area Change at baseline and 3 months was 33.9 ± 13.8 and 33.5 ± 10.7 p = 0.9 in the HPSD group while 38.1 ± 8.6 and 35.3 ± 12.2 p = 0.9 in the CB2 group. LA Ejection Fraction measured in the two groups (before and 3-month post-procedure): HPSD: 51.2 ± 20.5% and 49.5 ± 14.7%, p = 0.9, CB2: 49.7 ± 15.5% and 50.7 ± 13.3%, p = 0.8). Ablation time was comparable in the two groups (HPSD: 1676 ± 570 sec, CB2: 1495 ± 494 sec, p = 0.279), while fluoroscopy time and radiation exposure were significantly higher in the CB2 group (HPSD: 5.62 ± 4.31 min and 232 ± 406 cGycm2, CB2: 13.65 ± 5.18 min and 1819 ± 1669 cGycm2, p &amp;lt;0.001 and p &amp;lt;0.001). The LVA/LA surface ratio were: HPSD group: 8.37 ± 6.42% and CB2 group: 13.58 ± 8.92% (p = 0.007). At 12-month follow-up, the success rate, defined as freedom from AF/atrial tachycardia without antiarrhythmic drug was 80.1% (HPSD) and 84.2% (CB2) respectively. Conclusions The LA scar tissue was significantly higher following CB2 ablation, but did not affect medium-term efficacy. However, tissue loss did not reduce the transport function of the LA.

Atrial tissue characterization by cardiac magnetic resonance and high-density mapping in patients with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Left atrial fibrosis is a marker of atrial disease and it has an important role in the pathophysiology of atrial fibrillation (AF). Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is an emerging tool to detect left atrial fibrosis. However, data on the correlation between LGE-CMR detected fibrosis and low voltage areas to define fibrotic tissue is scarce. PURPOSE To assess the correlation and degree of concordance between LGE-CMR and high-density bipolar voltage mapping for the identification of left atrial abnormal tissue. METHODS Seven patients scheduled for AF ablation (including first and redo procedures) underwent a preprocedural 1.5 Tesla LGE-CMR including left atrial 3D inversion-recovery steady-state free precession sequence (ECG and respiratory triggering) 20 minutes after the injection of 0.2 mmol/kg of gadobutrol. A high-density electroanatomical voltage mapping was acquired with a 16-electrode grid configuration mapping catheter during sinus rhythm. LGE-CMR studies were analyzed off-line with an advanced image post-processing tool (ADAS 3D). Atrial wall intensity was normalized to blood pool, obtaining an image intensity ratio (IIR) value for each CMR point of the 3D model. High-density bipolar voltage maps and LGE-CMR 3D left atrial reconstruction were merged (figure, panel A). Voltage points were projected to the LGE-CMR left atrial 3D model, allowing point-by-point correlation analysis between voltage (log transformed due to non-normal distribution) with IIR. Left atrial fibrosis area and percentage were quantified using the standard cut-off values (bipolar voltage &amp;lt;0.5mV and IIR &amp;gt;1.2). We assessed the degree of concordance for normal and abnormal (fibrosis) tissue classification between the two techniques using different cut-off values (&amp;lt; 0.5mV and &amp;lt;1mV for bipolar voltage and &amp;gt;0.9, &amp;gt;1, &amp;gt;1.1 and &amp;gt;1.2 for IIR). RESULTS The average fibrosis area detected with LGE-CMR was lower than that detected with high-density bipolar voltage, using standard cut-off values (18.6 ± 5.7 cm2 vs. 40.6 ± 12.5 cm2, p = 0.13 respectively). There was a poor global point-by-point correlation between log-transformed voltage and IIR was r=-0.093, p &amp;lt; 0.001 (figure, panel B). The best concordance was obtained when using bipolar voltage and IIR of 0.5mV and 1.2, respectively (64.7 %; Kappa 0.101). However, the highest kappa index (0.142) for concordance was achieved with cutoff values of bipolar voltage &amp;lt;1mV and IIR &amp;gt;1, with an agreement percentage of 54.6%. CONCLUSIONS Left atrial tissue characterization between LGE-CMR and high-density bipolar voltage mapping showed significant but poor point-by-point correlation. Although the highest concordance was obtained using standard cutoff values, the Kappa index was best when applying non-standard cutoffs (1mV for bipolar voltage and &amp;gt;1 for IIR). Abstract Figure.

Left atrial scar burden in sinus rhythm differs from atrial fibrillation using automated voltage analysis during radiofrequency ablation for atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Scar burden in atrial fibrillation (AF) can be overestimated due to many factors. Scar burden has prognostic value and substrates considered for ablation by some electrophysiologists. We compared left atrial (LA) scar voltage in AF to sinus rhythm (SR) using voltage histogram analysis (VHA) of those undergoing pulmonary vein isolation (PVI) for persistent AF (PeAF). We believe this is the first study analysing LA scar location in SR and AF using VHA. Methods We retrospectively analysed 120 anatomical segments (AS) and whole LA voltages (N= 10 patients, mean age 68 ± 7, 4 females) in SR and AF. Fast anatomical maps (FAM) were grouped into 6 AS in AF and SR: Anterior, Posterior, Roof, Floor, Septal and Lateral AS, which were analysed via VHA (Figure 1) in 10 voltage ranges between 0mV-0.5mV. Total LA area in each voltage aliquot was recorded in SR and AF, taking diseased LA as 0.2-0.5mV and dense LA scar as &amp;lt;0.2mV. The pulmonary veins, mitral annulus and trans-septal puncture sites were excluded from analyses. We included patients over age 18 with PeAF who had de novo PVI with no extra ablation lines, maps with &amp;gt;1000 voltage points in both rhythms and uniform procedure involving initial mapping in AF then remapping in SR after PVI. Statistical analyses conducted with IBM SPSS v.26. Results Total LA scar burden was greater in AF (Mean 142.76 mm², SD ± 138.78mm²) than SR (Mean 109mm², SD ± 107.8mm²), p= &amp;lt;0.0001, Table 1. Scar correlation in SR and AF had a good relationship, R = 0.416 (p= &amp;lt;0.001). Every 1mm² of scar identified during SR yielded a mean of 1.54mm² in AF, (p= &amp;lt;0.001). Conclusions AF was associated with higher scar burden in the Roof, Anterior, Lateral and Posterior AS. Dense LA scar (≤ 0.2mV) on the Posterior AS was significantly higher in AF, while in other AS was comparable to SR. Mapping substrate in AF, especially the posterior wall, may be misleading as scar burden may be overestimated when compared to SR. Table 1Voltage&amp;lt; 0.02 mV (mean area ± SD mm2)0.2-0.5mV (mean area mm2)RhythmSRAFp-valueSRAFp-valueEntire LA115.89 ± 113.61143.41 ± 144.230.02*105.78 ± 103.73144.00 ± 135.24&amp;lt;0.0001*Roof82.72 ± 117.3283.68 ± 113.560.95115 ± 77.14150.61 ± 93.170.01*Anterior131.8 ± 169.53126.5 ± 154.570.85158.53 ± 99.22220.87 ± 173.070.002*Lateral70.5 ± 80.0090.57 ± 117.990.3687.52 ± 66.82137.05 ± 104.990.0002*Septal80.99 ± 89.0380.99 ± 89.030.6899.123 ± 73.62115.37 ± 84.830.18Floor105.1 ± 134.91106.42 ± 148.670.96117.62 ± 85.41151.2 ± 110.070.052Posterior102.14 ± 157.47159.03 ± 194.650.02*138.27 ± 112.28234 ± 150.45&amp;lt;0.0001*LA scar distribution in SR and AF, *denotes significant results.Abstract Figure 1

Prognostic Value of Pulmonary Transit Time and Pulmonary Blood Volume Estimation Using Myocardial Perfusion CMR

ObjectivesThe purpose of this study was to explore the prognostic significance of PTT and PBVi using an automated, inline method of estimation using CMR. BackgroundPulmonary transit time (PTT) and pulmonary blood volume index (PBVi) (the product of PTT and cardiac index), are quantitative biomarkers of cardiopulmonary status. The development of cardiovascular magnetic resonance (CMR) quantitative perfusion mapping permits their automated derivation, facilitating clinical adoption. MethodsIn this retrospective 2-center study of patients referred for clinical myocardial perfusion assessment using CMR, analysis of right and left ventricular cavity arterial input function curves from first pass perfusion was performed automatically (incorporating artificial intelligence techniques), allowing estimation of PTT and subsequent derivation of PBVi. Association with major adverse cardiovascular events (MACE) and all-cause mortality were evaluated using Cox proportional hazard models, after adjusting for comorbidities and CMR parameters. ResultsA total of 985 patients (67% men, median age 62 years [interquartile range (IQR): 52 to 71 years]) were included, with median left ventricular ejection fraction (LVEF) of 62% (IQR: 54% to 69%). PTT increased with age, male sex, atrial fibrillation, and left atrial area, and reduced with LVEF, heart rate, diabetes, and hypertension (model r2 = 0.57). Over a median follow-up period of 28.6 months (IQR: 22.6 to 35.7 months), MACE occurred in 61 (6.2%) patients. After adjusting for prognostic factors, both PTT and PBVi independently predicted MACE, but not all-cause mortality. There was no association between cardiac index and MACE. For every 1 × SD (2.39-s) increase in PTT, the adjusted hazard ratio for MACE was 1.43 (95% confidence interval [CI]: 1.10 to 1.85; p = 0.007). The adjusted hazard ratio for 1 × SD (118 ml/m2) increase in PBVi was 1.42 (95% CI: 1.13 to 1.78; p = 0.002). ConclusionsPulmonary transit time (and its derived parameter pulmonary blood volume index), measured automatically without user interaction as part of CMR perfusion mapping, independently predicted adverse cardiovascular outcomes. These biomarkers may offer additional insights into cardiopulmonary function beyond conventional predictors including ejection fraction.

The association between transthoracic echocardiogram parameters and white matter hyperintensities

ObjectiveIdentify abnormal cardiac chamber size and hemodynamic parameters on transthoracic echocardiogram (TTE) as predictors of advancing cerebral small vessel disease (CSVD) on brain magnetic resonance imaging (MRI). Materials and methodsA retrospective chart review of adults with a brain MRI and a 2-dimensional TTE was performed. WMH measured by the Fazekas score served as the primary outcome. We fit multivariate ordinal logistic regression models to the Fazekas score with the individual predictors of the TTE measurements and adjusted for potential confounders. Results132 individuals were included. Cardiac functional markers were not significant, including tricuspid annular plane systolic excursion (p = 0.818), right ventricular ejection fraction (p = 0.818) and left ventricular ejection fraction (p = 0.673). Cardiac structural markers included right atrial area (p = 0.247), right ventricular internal diameter (RVID, p = 0.020) and left atrial area (LAA, p = 0.041). RVID and LAA were identified as being predictors, although the direction of the association suggested that normal values resulted in more WMH. Analysis of isolated DWM or PVWM Fazekas scores were not associated with cardiac structure or function. ConclusionsIn our study, we found that normal LAA and RVID values were associated with an increased degree of WMH on MRI. This finding may represent earlier identification of WMH prior to TTE cardiac changes. Future studies are needed for more robust quantitative comparison as well as evaluation prospectively of the association between cardiac chamber sizes and development of WMH.

Echocardiographic diagnosis of atrial cardiomyopathy allows outcome prediction following pulmonary vein isolation

BackgroundRelevant atrial cardiomyopathy (ACM), defined as a left atrial (LA) low-voltage area ≥ 2 cm2 at 0.5 mV threshold on endocardial contact mapping, is associated with new-onset atrial fibrillation (AF), higher arrhythmia recurrence rates after pulmonary vein isolation (PVI), and an increased risk of stroke. The current study aimed to assess two non-invasive echocardiographic parameters, LA emptying fraction (EF) and LA longitudinal strain (LAS, during reservoir (LASr), conduit (LAScd) and contraction phase (LASct)) for the diagnosis of ACM and prediction of arrhythmia outcome after PVI.MethodsWe prospectively enrolled 60 consecutive, ablation-naive patients (age 66 ± 9 years, 80% males) with persistent AF. In 30 patients (derivation cohort), LA-EF and LAS cut-off values for the presence of relevant ACM (high-density endocardial contact mapping in sinus rhythm prior to PVI at 3000 ± 1249 sites) were established in sinus rhythm and tested in a validation cohort (n = 30). Arrhythmia recurrence within 12 months was documented using 72-h Holter electrocardiograms.ResultsAn LA-EF of < 34% predicted ACM with an area under the curve (AUC) of 0.846 (sensitivity 69.2%, specificity 76.5%) similar to a LASr < 23.5% (AUC 0.878, sensitivity 92.3%, specificity 82.4%). In the validation cohort, these cut-offs established the correct diagnosis of ACM in 76% of patients (positive predictive values 87%/93% and negative predictive values 73%/75%, respectively). Arrhythmia recurrence in the entire cohort was significantly more frequent in patients with LA-EF < 34% and LASr < 23.5% (56% vs. 29% and 55% vs. 26%, both p < 0.05).ConclusionThe echocardiographic parameters LA-EF and LAS allow accurate, non-invasive diagnosis of ACM and prediction of arrhythmia recurrence after PVI.Graphic abstract

The Prognostic Value of Left Atrial Reservoir Functional Indices Measured by Three-Dimensional Speckle-Tracking Echocardiography for Major Cardiovascular Events.

Left atrial (LA) volume and left ventricular longitudinal strain (LVLS) have significant prognostic values for major cardiovascular events (MACEs). Prognostic values of LA reservoir functional indices measured by 3-dimensional (3D) speckle-tracking echocardiography (STE) were evaluated. A total of 264 patients, who underwent 2-dimensional (2D) echocardiography and 3DSTE for various underlying heart diseases, were followed up to record MACE. After a mean follow up of 547±435 days, 30 patients developed MACE: 7 cardiac deaths, 6 strokes, 1 non-fatal myocardial infarction, and 22 admissions for heart failure (5 of these had cardiac death after discharge, whereas 1 sustained stroke after discharge). Receiver operating characteristic curve analysis was performed to determine the optimal cut-off levels of 4 LA functional indices: LA emptying fraction (LAEmpF), LA longitudinal strain (LALS), LA circumferential strain (LACS), and LA area change ratio (LAAC), using 3DSTE. Among these factors, 2DLVLS, 3DLAEmpF, and 3DLALS demonstrated a higher hazard ratio (>5.0) than other variables. The 3DLAEmpF and 3DLALS had a higher average treatment effect (ATE) and ATE on the treated (ATT), respectively, than the other indices after propensity score matching. Addition of 3DLAEmpF to the base model using clinical variables and LV ejection fraction or 2DLVLS demonstrated higher prognostic power. LAEmpF calculated using 3DSTE possessed additive prognostic values for the prediction of MACE.

Impact of the new definition of pulmonary hypertension according to world symposium of pulmonary hypertension 2018 on diagnosis of post-capillary pulmonary hypertension

Background:The World Symposium on Pulmonary Hypertension (WSPH) in 2018 recommended new definitions of pulmonary hypertension (PH). We investigated the impact of the updated definition on prevalence of PH due to left heart disease (PH-LHD).Methods:The data of right heart catheterizations in patients with suspected PH-LHD between January 2008 and July 2015 was retrospectively analyzed applying different definitions. The number of patients diagnosed by the updated WSPH hemodynamic criteria of a mean pulmonary artery pressure (mPAP) > 20 mmHg was compared to the number of patients using mPAP ≥ 25 mmHg. The differentiation between patients with isolated post-capillary (Ipc) and combined post-capillary and pre-capillary (Cpc) PH was analyzed comparing the ESC/ERS guidelines, the recommendation of Cologne Consensus Conference (CCC) and WSPH.Results:Of the 726 patients with a suspected PH, 58 patients met the diagnostic criteria of the ESC/ERS guidelines for PH-LHD with 32.8% Ipc-cases, 34.4% Cpc-PH-cases and 32.8% unclassifiable cases. Overall, 58 patients were diagnosed by the CCC criteria, with 34.5% classified as Cpc-PH and 65.5% as Icp-PH. Using the criteria of WSPH, the number of PH-LHD rose by one patient. According to the new definition, 64.4% of the patients were classified as Cpc-PH and had a significantly higher right to left atrial area (RA/LA) ratio than Ipc-PH patients.Conclusion:Applying the new recommendation, the number of diagnosed patients with PH-LHD increases marginally. There is, however, a relevant shift in the number of Cpc-PH cases. An elevated RA/LA ratio might help to identify patients for invasive diagnostic work-up.

Implications of Atrial Fibrillation on the Mechanisms of Mitral Regurgitation and Response to MitraClip in the COAPT Trial.

Atrial fibrillation (AF), mitral regurgitation (MR), and left ventricular (LV) ejection fraction have a complex interplay. We evaluated the role of AF in patients with heart failure and moderate-to-severe or severe secondary MR enrolled in the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) and its impact on mechanisms and outcomes with the MitraClip. Patients in the COAPT trial were stratified by the presence (n=327) or absence (n=287) of a history of AF and by assignment to treatment group. Clinical, echocardiographic, and outcome measures were assessed. The primary outcome was the composite rate of death or heart failure hospitalization at 24 months. Patients with history of AF were older and more often male. They had a higher LV ejection fraction, larger left atrial volumes and mitral valve orifice areas, smaller LV volumes, and similar MR severity. Patients with AF compared with those without a history of AF had a higher unadjusted (hazard ratio [HR], 1.32 [95% CI, 1.06–1.64], P=0.01) and adjusted (HR, 1.30 [1.03–1.64], P=0.03) 2-year rate of the primary outcome. Treatment with the MitraClip compared with guideline-directed medical therapy alone reduced death or heart failure hospitalization in both those with (HR, 0.61 [0.46–0.82]) and without (HR, 0.46 [0.33–0.66]) a history of AF (Pint=0.18). Treatment with the MitraClip was associated with a lower risk of stroke in patients with a history of AF (HR, 0.18 [0.04–0.86]) but not in those without a history of AF (HR, 1.64 [0.58–4.62]; Pint=0.02). In the COAPT trial, patients with a history of AF had larger left atrial and mitral valve orifice areas with higher LV ejection fraction and smaller LV volumes, suggesting an atrial mechanism contribution to functional MR. Despite the worse prognosis of heart failure patients with a history of AF, MR reduction with the MitraClip still afforded substantial clinical benefits. Treatment with MitraClip was associated with a lower risk of stroke in patients with a history of AF. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Atrial fibrillation risk scores to evaluate left atrial substrate based on voltage analysis in long-standing persistent type of arrhythmia.

Pre-ablation identification of left atrial (LA) low voltage areas (LVA) among long-standing persistent atrial fibrillation (LSPAF) population remains challenging. The aim of the study was to analyze the potential of selected scores originally developed to assess arrhythmia recurrences, thromboembolic complications, or progression from paroxysmal to persistent AF to predict the presence of LA-LVA in LSPAF patients. One hundred and fifty-two patients underwent pulmonary vein isolation followed by high-density-high-resolution LA voltage mapping. AF risk scores, such as APPLE, ATLAS, CAAP-AF, DR-FLASH, CHA2DS2-VASc, and HATCH were retrospectively calculated. A receiver operating characteristic curve analysis was performed to evaluate the ability of the scores to predict LVA. Low voltage areas were detected in 52% of the patients. 28% of the patients with LVA presented severe global LVA burden, whereas 56% of the patients showed a disseminated pattern of remodeling. CAAP-AF ≥7, DR-FLASH ≥4, and CHA2DS2-VASc ≥3 predicted the presence of LVA, whereas ATLAS ≤7 indicated the absence of LVA. ATLAS ≤8, CAAP-AF ≤9, DR-FLASH ≤4, and CHA2DS2-VASc ≤3 predicted the absence of severe LVA. APPLE ≤3 and CHA2DS2-VASc ≤2 predicted the absence of a LVA disseminated pattern. Among predictive scores, ATLAS (AUC, 0.633, 95% CI, 0.543-0.723, P = 0.004), DR-FLASH (AUC, 0.696; 95% CI, 0.594-0.81; P <0.001), and CHA2DS2-VASc (AUC, 0.644; 95% CI 0.518-0.77; P = 0.025) were the best predictors for the absence of LVA, severe LVA and a disseminated pattern of LVA, respectively. Atrial fibrillation risk stratification with specific scoring systems can unmask the presence of LA-LVA in the LSPAF population.

Natriuretic peptide release during exercise in patients with valvular heart disease: A systematic review.

Serum biomarkers have a potential role in the risk stratification of patients with heart valve disease and may help determine the optimal timing of intervention. Much of the published literature relates to biomarker sampling in a resting state, but the relationship of exercise biomarkers is less well described. We performed a systematic review to examine the significance of exercise natriuretic peptides on echocardiographic variables and cardiovascular events, in valvular heart disease. A search for studies that assessed exercise biomarkers in patients with moderate to severe valve lesions was performed. We examined the relationship between rest and exercise BNP and also the endpoints of symptoms, haemodynamic or echocardiographic variables and clinical outcomes. Eleven prospective studies were identified (844 participants). 61% were male and the mean age was 55.2 ± 9.6 years. The majority of the blood samples were taken at baseline and within 3 minutes of stopping exercise. There was a significant increase in exercise BNP compared with rest, in patients with aortic stenosis, mitral regurgitation and mitral stenosis. Elevated exercise BNP levels correlated with mean gradient and left atrial area, and there was a relationship between a higher exercise BNP and a blunted blood pressure response, in aortic stenosis. Furthermore, exercise BNP was independently associated with cardiac events, over and above resting values, in patients with mitral regurgitation and aortic stenosis. The results suggesting that exercise natriuretic peptide levels may have additive prognostic importance over resting levels, as well as demographic and echocardiographic data.

Associations Between HIV Serostatus and Cardiac Structure and Function Evaluated by 2-Dimensional Echocardiography in the Multicenter AIDS Cohort Study.

BackgroundWe aimed to investigate whether there are differences in cardiac structure and systolic and diastolic function evaluated by 2‐dimensional echocardiography among men living with versus without HIV in the era of combination antiretroviral therapy.Methods and ResultsWe performed a cross‐sectional analysis of 1195 men from MACS (Multicenter AIDS Cohort Study) who completed a transthoracic echocardiogram examination between 2017 and 2019. Associations between HIV serostatus and echocardiographic indices were assessed by multivariable regression analyses, adjusting for demographics and cardiovascular risk factors. Among men who are HIV+, associations between HIV disease severity markers and echocardiographic parameters were also investigated. Average age was 57.1±11.9 years; 29% of the participants were Black, and 55% were HIV+. Most men who were HIV+ (77%) were virally suppressed; 92% received combination antiretroviral therapy. Prevalent left ventricular (LV) systolic dysfunction (ejection fraction <50%) was low and HIV serostatus was not associated with left ventricular ejection fraction. Multivariable adjustment models showed that men who were HIV+ versus those who were HIV− had greater LV mass index and larger left atrial diameter and right ventricular (RV) end‐diastolic area; lower RV function; and higher prevalence of diastolic dysfunction. Higher current CD4+ T cell count ≥400 cell/mm3 versus <400 was associated with smaller LV diastolic volume and RV area. Virally suppressed men who were HIV+ versus those who were HIV− had higher indexed LV mass and left atrial areas and greater diastolic dysfunction.ConclusionsHIV seropositivity was independently associated with greater LV mass index, left atrial and RV sizes, lower RV function and diastolic abnormalities, but not left ventricular ejection fraction, which may herald a future predisposition to heart failure with preserved ejection fraction among men living with HIV.