A systematic review and meta-analysis of left atrial strain in hypertrophic cardiomyopathy and its prognostic utility.

Despite advances in noninvasive imaging modalities to identify atrial fibrillation (AF) risk in Hypertrophic Cardiomyopathy (HCM), there is a paucity of evidence concerning the impact of low Left Atrial strain (LAS) on AF and major adverse cardiac events (MACE) incidence in these patients. This study investigated the diagnostic and prognostic significance of LAS in predicting AF and MACE in HCM. Findings revealed lower LA reservoir (MD: -11.79, 95% CI -14.83, -8.74; p<0.00001), booster (MD: -4.10, 95% CI -6.29, -1.91; p=0.0002), and conduit (MD: -7.52, 95% CI -9.39, -5.65; p<0.00001) strains in HCM patients versus healthy controls, and also indicated a significant association between low LA reservoir/conduit/booster strain and the development of new AF as well as MACE prevalence in HCM patients. The results from this study suggest the valuable role of LA strain in HCM and its utility in predicting the development of new AF and cardiac events in HCM patients.

Impact of late gadolinium enhancement extent, location, and pattern on ventricular tachycardia and major adverse cardiac events in patients with ischemic vs. non-ischemic cardiomyopathy.

Background: Left ventricular late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) has been associated with increased risk for life-threatening ventricular tachyarrhythmias. The differences in association between LGE characteristics and prognosis in patients with ischemic (ICM) vs. non-ischemic (NICM) cardiomyopathy is incompletely understood. Methods: A total of 168 consecutive patients who underwent CMR imaging with either ICM or NICM were included in our study. LGE extent, location and pattern were examined for association to the primary endpoint of ventricular tachycardia (VT) and secondary endpoint of major adverse cardiac events (MACE). Results: Of 68 (41%) patients with ICM and 97 (59%) patients with NICM, median LGE mass was 15% (IQR 9-28) for the ICM group and 10% (IQR 6-15) for the NICM group. On multivariate analysis for both groups, LGE characteristics were prognostic while LVEF was not. In patients with ICM, septal and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median) and inferior wall LGE independently predicted the primary endpoint. In patients with NICM, anterior, inferior and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median, number of LGE segments, LGE stratified per 5% increase) and midwall LGE were independent predictors of the primary endpoint. Conclusions: Although LGE was an independent predictor of prognosis in both groups, LGE extent, location, and pattern characteristics were more powerful correlates to worse outcomes in patients with NICM than ICM.

Association of left atrial strain by cardiovascular magnetic resonance with recurrence of atrial fibrillation following catheter ablation.

BACKGROUND: Atrial fibrillation (AF) is a progressive condition, which is characterized by inflammation/fibrosis of left atrial (LA) wall, an increase in the LA size/volumes, and decrease in LA function. We sought to investigate the relationship of anatomical and functional parameters obtained by cardiovascular magnetic resonance (CMR), with AF recurrence in paroxysmal AF (pAF) patients after catheter ablation. METHODS: We studied 80 consecutive pAF patients referred for ablation, between January 2014 and December 2019, who underwent pre- and post-ablation CMR while in sinus rhythm. LA volumes were measured using the area-length method and included maximum, minimum, and pre-atrial-contraction volumes. CMR-derived LA reservoir strain (ℇR), conduit strain (ℇCD), and contractile strain (ℇCT) were measured by computer assisted manual planimetry. We used a multivariate logistical regression to estimate the independent predictors of AF recurrence after ablation. RESULTS: Mean age was 58.6 ± 9.4 years, 75% men, mean CHA2DS2-VASc score was 1.7, 36% had prior cardioversion and 51% were taking antiarrhythmic drugs. Patients were followed for a median of 4 years (Q1-Q3 = 2.5-6.2 years). Of the 80 patients, 21 (26.3%) patients had AF recurrence after ablation. There were no significant differences between AF recurrence vs. no recurrence groups in age, gender, CHA2DS2-VASc score, or baseline comorbidities. At baseline, patients with AF recurrence compared to without recurrence had lower LV end systolic volume index (32 ± 7 vs 37 ± 11 mL/m2; p = 0.045) and lower ℇCT (7.1 ± 4.6 vs 9.1 ± 3.7; p = 0.05). Post-ablation, patients with AF recurrence had higher LA minimum volume (68 ± 32 vs 55 ± 23; p = 0.05), right atrial volume index (62 ± 20 vs 52 ± 19 mL/m2; p = 0.04) and lower LA active ejection fraction (24 ± 8 vs 29 ± 11; p = 0.05), LA total ejection fraction (39 ± 14 vs 46 ± 12; p = 0.02), LA expansion index (73.6 ± 37.5 vs 94.7 ± 37.1; p = 0.03) and ℇCT (6.2 ± 2.9 vs 7.3 ± 1.7; p = 0.04). Adjusting for clinical variables in the multivariate logistic regression model, post-ablation minimum LA volume (OR 1.09; CI 1.02-1.16), LA expansion index (OR 0.98; CI 0.96-0.99), and baseline ℇR (OR 0.92; CI 0.85-0.99) were independently associated with AF recurrence. CONCLUSION: Significant changes in LA volumes and strain parameters occur after AF ablation. CMR derived baseline ℇR, post-ablation minimum LAV, and expansion index are independently associated with AF recurrence.

Comparison of left atrial strain by feature-tracking cardiac magnetic resonance with speckle-tracking transthoracic echocardiography.

Left atrial (LA) strain is a novel non-invasive parameter for assessing LA hemodynamics and function. We sought to compare the intermodality differences between transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) derived LA strain, as well as reproducibility of strain measurements. We evaluated 70 subjects (mean age 42.1 ± 17 years, 44% males) with no significant cardiovascular disease who underwent both CMR and TTE within 6 months of each other. LA strain measurements i.e. reservoir strain (ƐR), conduit strain (ƐCD), and contractile strain (ƐCT), were compared using speckle-tracking echocardiography (STE) and CMR feature tracking (CMR-FT). Correlation and systematic bias between modalities was evaluated using intraclass correlation coefficient (ICC) and proportional bias. TTE was performed before CMR with a median duration of 33 days (IQR 14-69 days). ICC for ƐR, ƐCT, ƐCD was 0.66 (95% CI 0.44-0.79), 0.63 (95% CI 0.4-0.77) and 0.56 (95% CI 0.3-0.73) respectively. There was evidence of systematic bias between modalities, on average LA volume was found to be 19% higher on CMR than TTE. Strain values were also higher by CMR-FT compared to STE with mean difference of 9.9 ± 12 (26.1%), 3.1 ± 5.5 (21.9%), 4.0 ± 9.9 (16.6%) for ƐR, ƐCT and ƐCD respectively. Regression showed proportional bias for both ƐR, and ƐCT (beta 0.76, 0.54 respectively; P < 0.0001). There were modest differences in intraobserver reproducibility between both modalities with better reproducibility for STE compared to CMR-FT. There was a modest intermodality correlation between STE and CMR-FT derived LA strain components. There were systematic differences and proportional bias in measurements between modalities. These differences should be considered when interpreting LA strain using either modality.

Paradoxical Embolism Causing Myocardial Infarction in a COVID-19 Patient Presenting With Pulmonary Embolism.

The presence of myocardial injury in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is common. The cardiac complications of SARS-CoV2 infection are varied and distinguishing between them can be complicated.  A 55-year-old man with recent diagnosis of SARS-CoV2 infection presented with chest pain, syncope, and was found to have saddle pulmonary embolism (PE). Marked elevation in cardiac enzymes prompted a coronary angiogram which was normal. Cardiac MRI revealed late gadolinium enhancement (LGE) in the anterolateral wall consistent with myocardial infarction (MI). He was diagnosed with paradoxical embolism causing MI. The differential for elevated cardiac enzymes is wide in patients with SARS-CoV2 infection. This case illustrates that sometimes multiple diagnoses exist, and that a high index of suspicion is required to continue work-up.

Association of Cardiomyopathy With MYBPC3 D389V and MYBPC3Δ25bpIntronic Deletion in South Asian Descendants.

Importance: The genetic variant MYBPC3Δ25bp occurs in 4% of South Asian descendants, with an estimated 100 million carriers worldwide. MYBPC3 Δ25bp has been linked to cardiomyopathy and heart failure. However, the high prevalence of MYBPC3Δ25bp suggests that other stressors act in concert with MYBPC3Δ25bp. Objective: To determine whether there are additional genetic factors that contribute to the cardiomyopathic expression of MYBPC3Δ25bp. Design, Setting, andParticipants: South Asian individuals living in the United States were screened for MYBPC3Δ25bp, and a subgroup was clinically evaluated using electrocardiograms and echocardiograms at Loyola University, Chicago, Illinois, between January 2015 and July 2016. Main Outcomes and Measures: Next-generation sequencing of 174 cardiovascular disease genes was applied to identify additional modifying gene mutations and correlate genotype-phenotype parameters. Cardiomyocytes derived from human-induced pluripotent stem cells were established and examined to assess the role of MYBPC3Δ25bp. Results: In this genotype-phenotype study, individuals of South Asian descent living in the United States from both sexes (36.23% female) with a mean population age of 48.92 years (range, 18-84 years) were recruited. Genetic screening of 2401 US South Asian individuals found an MYBPC3Δ25bpcarrier frequency of 6%. A higher frequency of missense TTN variation was found in MYBPC3Δ25bp carriers compared with noncarriers, identifying distinct genetic backgrounds within the MYBPC3Δ25bp carrier group. Strikingly, 9.6% of MYBPC3Δ25bp carriers also had a novel MYBPC3 variant, D389V. Family studies documented D389V was in tandem on the same allele as MYBPC3Δ25bp, and D389V was only seen in the presence of MYBPC3Δ25bp. In contrast to MYBPC3Δ25bp, MYBPC3Δ25bp/D389V was associated with hyperdynamic left ventricular performance (mean [SEM] left ventricular ejection fraction, 66.7 [0.7%]; left ventricular fractional shortening, 36.6 [0.6%]; P < .03) and stem cell-derived cardiomyocytes exhibited cellular hypertrophy with abnormal Ca2+ transients. Conclusions and Relevance: MYBPC3Δ25bp/D389V is associated with hyperdynamic features, which are an early finding in hypertrophic cardiomyopathy and thought to reflect an unfavorable energetic state. These findings support that a subset of MYBPC3Δ25bp carriers, those with D389V, account for the increased risk attributed to MYBPC3Δ25bp.

High-Throughput Diagnostic Assay for a Highly Prevalent Cardiomyopathy-Associated MYBPC3 Variant.

A 25-basepair deletion variant of MYBPC3 occurs at high frequency in individuals of South Asian descent and is estimated to affect 55 million people worldwide, carrying an increased likelihood of cardiomyopathy. Since this variant is prevalent and severe in this subpopulation, quick and affordable screening to provide risk-assessment to guide treatment for these patients is critical. An RNaseH qPCR assay was developed to quickly and specifically diagnose the presence of the 25-basepair deletion variant in MYBPC3. RNAseH-blocked nucleotide primers were designed to identify the presence or absence of the wild type MYBPC3 allele or the genomic sequence containing the 25-basepair deletion. Using this assay, three blinded operators were able to accurately determine the genotype from human genomic DNA samples from blood and saliva using a qPCR thermocycler. Furthermore, positive variant subjects were examined by both electrocardiography and echocardiography for the presence of cardiomyopathy. A simple, robust assay was established, verified and validated that can be automated to detect the presence of the highly prevalent 25-basepair deletion MYBPC3 variant using both blood and saliva samples. The assay will provide quick and accurate prescreening of individuals at high risk for cardiomyopathies and allow for better clinical identification of 25-basepair deletion MYBPC3 carriers in large cohort epidemiological studies.

Left atrial volume assessment in atrial fibrillation using multimodality imaging: a comparison of echocardiography, invasive three-dimensional CARTO and cardiac magnetic resonance imaging.

Left atrial size in atrial fibrillation is a strong predictor of successful ablation and cardiovascular events. Cardiac magnetic resonance multislice method (CMR-MSM) is the current gold standard for left atrial volume (LAV) assessment but is time consuming. We investigated whether LAV with more rapid area-length method by echocardiography (Echo-AL) or cardiac magnetic resonance (CMR-AL) and invasive measurement by 3D-CARTO mapping during ablation correlate with the CMR-MSM. We studied 250 consecutive patients prior to atrial fibrillation ablation. CMR images were acquired on 3T scanner to measure LAV by MSM and biplane area-length method. Standard echocardiography views were used to calculate LAV by biplane area-length method. LAV during ablation was measured by 3D-CARTO mapping. LAV was compared using intra-class correlation (ICC), Pearson's correlation and Bland-Altman plots. CMR-MSM was used as the reference standard. Mean LAV using CMR-MSM was 112.7 ± 36.7 ml. CMR-AL method overestimated LAV by 13.3 ± 21.8 ml (11.2%, p < 0.005) whereas 3D-CARTO and Echo-AL underestimated LAV by 8.3 ± 22.6 and 24.0 ± 27.6 ml respectively (8.7% and 20.0% respectively, p < 0.005). There was no significant difference between paroxysmal and persistent atrial fibrillation. CMR-AL and 3D-CARTO correlated and agreed well with CMR-MSM (r = 0.87 and 0.74, ICC = 0.80 and 0.77 respectively). However, Echo-AL had poor correlation and agreement with CMR-MSM (r = 0.66 and ICC = 0.48). Bland-Altman plots confirmed these findings. CMR-AL method may be used as an alternative to CMR-MSM, as it is non-invasive, rapid, and correlates well with CMR-MSM. LAV by different modalities should not be used interchangeably.

Importance of three-dimensional geometric analysis in the assessment of the athlete's heart.

How the left ventricle remodels in response to a high-volume stimulus is important in evaluating the endurance athlete's heart. Marathoners and patients with isolated, moderate chronic compensated mitral regurgitation (MR) represent physiologic and pathologic forms of eccentric left ventricular (LV) remodeling in response to intermittent and chronic volume overload, respectively. Thus, in this study, magnetic resonance imaging with tissue tagging and 3-dimensional data analysis at rest were performed in 19 marathoners (mean age 39 ± 10 years, 47% women), 17 patients with isolated MR without coronary artery disease or medical therapy (mean age 46 ± 5 years, 53% women), and 24 controls (mean age 45 ± 8 years, 50% women). Marathoners and patients with MR had approximately 35% greater LV end-diastolic volume indexes, approximately 50% greater end-systolic volume indexes, and approximately 34% greater LV stroke volume indexes (p <0.0001) compared to controls. However, marathoners' hearts had increased long-axis length, while those of patients with MR did not differ from the hearts of controls. The hearts of patients with MR had greater LV global and apex sphericity compared to those of marathoners and controls (p <0.0001). Marathoners had normal LV mass/volume ratios and wall thicknesses, whereas these were significantly decreased in the MR group. In marathoners, the baseline LV work rate was similar to that in controls and higher in patients with MR compared to controls. In conclusion, marathoners' hearts achieve elevated stroke volume at rest with adherence to an elliptical shape defined by 3-dimensional geometry and mass/volume ratio. Thus, a comprehensive evaluation of LV geometry and mass/volume ratio may be important in the evaluation of the athlete's heart.

Left atrial mechanical responses to right ventricular pacing in heart failure patients: implications for atrial fibrillation.

BACKGROUND: RV pacing (RVP), even with preserved atrioventricular (AV) synchrony, may lead to left atrial (LA) enlargement and atrial fibrillation. However, inciting events are unknown. We hypothesized that RVP acutely impairs LA function by mechanisms affecting atrial contraction and/or ventricular diastole. METHODS: LA function in ICD patients (n = 31, LVEF ≤ 40%) and controls (n = 14, LVEF > 50%) was contrasted between intrinsic conduction versus RVP during asynchronous (ICD, n = 17, control, n = 7), and synchronous (ICD, n = 14, control, n = 14) pacing at long (LAVd, 107 ±16 ms) and short (SAVd, 31 ± 5 ms) AV delays. LA maximal volume (LA(Max)), minimal volume (LA(Min)), and emptying fraction {LA(EmF) = (LA(Max) -LA(Min))/LA(Max)} were measured echocardiographically. Six-segment mean mitral annular tissue doppler E' (global E') assessed diastolic recoil during baseline and LAVd. RESULTS: In the ICD group, LA(Min) increased by 42% (P < 0.0009) during VVI, by 31% (P = 0.0002) during SAVd, and by 17% (P < 0.0007) during LAVd. LA(EmF) decreased by 44% (P < 0.0008), 27% (P < 0.0001), and by 15% (P = 0.003) during VVI, SAVd, and LAVd respectively. LA(Max) was unaltered. Global E' was reduced by 12%. In control, LA(Min) increased and LA(EmF) decreased significantly during VVI (82 and 58%) and SAVd (46 and 41%), but not during LAVd. CONCLUSION: In patients with LV dysfunction, RVP acutely impaired LA emptying, and increased minimal volume, most prominently when atrial contraction was impeded (VVI, DDD-SAVd) but also when completed (DDD-LAVd), indicating impaired diastolic recoil as an important mechanism. When LV function was normal, similar changes were present when atrial filling is impeded (VVI, SAVd), but not when completed (LAVd).

Mitral valve prolapse with a late-systolic regurgitant murmur may be associated with significant hemodynamic consequences.

The late-systolic murmur of mitral regurgitation (MR) in degenerative mitral valve disease is widely believed to represent regurgitation of a degree that is not associated with hemodynamic significance. However, the extent of left ventricular (LV) remodeling associated with the late-systolic murmur has not been systematically assessed. Accordingly, we studied 82 patients sent for evaluation of at least moderate isolated MR by echocardiography/Doppler examination. All patients had a physical examination and cardiac magnetic resonance imaging to measure LV volumes by summation of serial short-axis slices. Forty-five patients had a pan-systolic murmur and 37 had a late-systolic murmur on auscultation that was verified by timing of onset of regurgitant turbulence by cine magnetic resonance imaging. Systolic blood pressures (124 +/- 3 versus 124 +/- 3 mm Hg) and LV ejection fraction (61 +/- 1% versus 61 +/- 1%) did not differ significantly between pan-systolic and late-systolic murmur groups. Although LV end-diastolic volume index was greater in the pan-systolic versus late-systolic murmur (108 +/- 4 versus 95 +/- 4 mL/m2, P = 0.007), both groups were significantly greater than normals (68 +/- 2 mL/m2, P < 0.0001). However, LV end-systolic volume index (42 +/- 2 versus 38 +/- 2 mL/m2) and LV end-systolic dimension (38 +/- 1 versus 37 +/- 1 mm), critical markers of adverse LV remodeling in isolated MR, did not differ significantly between pan-systolic and late-systolic murmur groups. In conclusion, the late systolic isolated MR murmur may be associated with significant adverse LV remodeling, and should not be considered evidence of hemodynamically unimportant MR.

A new angle on the Angle of Louis.

Previous literature has stated that the center of the right atrium lies approximately 5 cm below the sternal angle regardless of body position. Our objective was to measure the distance from the Angle of Louis to various locations in the right atrium and determine whether these distances vary with patients' body habitus. The authors conducted a cross-sectional study with 52 consecutive patients who underwent computed tomography. The Angle of Louis was measured to various right atrial anatomic locations and was correlated with patients' body habitus characteristics. There was a positive correlation between patients' weight or body mass index and the distance of the Angle of Louis to right atrial locations. Therefore, using the traditional 5 cm in an obese patient can and usually will result in an underestimation of right atrial pressure. The authors suggest that in patients with body mass index > 35 kg/m2 (body surface area > 2.5 m2), a jugular venous column height at the clavicle is likely to indicate significantly elevated jugular venous pressure and should be considered abnormal. Therefore, further clinical assessment and subsequent therapeutic decisions of these morbidly obese patients with abnormal jugular venous pressures should be made accordingly.