Normal Left Ventricular Research Articles

Cardiomyocyte Specific MLK3 Deletion Opposes LV Dysfunction and Cardiac Fetal Gene Re-Expression

Study Objective: To determine the cardiac myocyte (CM) and blood pressure-independent effects of Mixed lineage kinase 3 (MLK3) in the regulation of left ventricular (LV) function at baseline and in response to pathological stress. Background: MLK3 functions as a direct substrate effector of cGMP-dependent protein kinase 1α (PKG1α). Whole-body MLK3 deletion in mice increases cardiac dysfunction and remodeling after pressure overload and prevents the therapeutic effect of cGMP augmentation on LV function. However, MLK3 deletion also causes hypertension, which may confound these findings. Hypothesis: MLK3 opposes LV dysfunction through a blood pressure-independent function in the cardiac myocyte (CM). Methods: We generated mice harboring LoxP sites flanking the MAP3K11 gene encoding MLK3 (MLK3fl/fl) and crossed them with αMHC-Cre transgenic mice, enabling constitutive postnatal cardiac myocyte-specific MLK3 deletion (CMKO). Male and female 3- and 6-month-old MLK3 CMKO and control MLK3 intact (MLK3fl/fl Cre-) littermates were studied in the basal state. We also performed transaortic constriction (TAC) or sham surgery for 4 weeks on 3-month-old male mice. We assessed LV structure and function by organ mass, echocardiography, pressure volume loop analysis, qPCR, and immunoblot. In basal and TAC studies, we used age-matched αMHC-Cre x MLK3+/+ (non-floxed) mice as additional controls. Results: MLK3 gene excision in CMs was confirmed by PCR. By 6 months of age, MLK3 CMKO mice displayed: progressive reduction in LV ejection fraction; increase in LV internal diameter; and LV hypertrophy, indicating LV dysfunction and pathological remodeling, compared with littermate controls or with αMHC-Cre x MLK3+/+ non-floxed mice. This effect was more prominent in females than in males. LV fetal gene expression did not differ between genotypes at 3 months. At 6 months of age, however, the fetal genes nppa, RCAN, and CTGF were significantly upregulated in both male and female MLK3 CMKO mice, compared with MLK3 intact, indicating pathological remodeling. After 4-week TAC, MLK3 CMKO LVs developed more severe reduction in LV systolic function compared with MLK3 intact littermates as assayed by echocardiographic measures of LV ejection fraction; and invasive hemodynamic indices of preload recruitable stroke work, maximum LV pressure and LV developed pressure. The MLK3 CMKO LVs also demonstrated a more eccentric remodeling phenotype in which LV mass/tibia length, LV end diastolic and end systolic diameters increased more severely in CMKO mice, with corresponding reduced LV wall thicknesses. Finally, lung mass/tibia length was elevated in the MLK3 CMKO TAC mice compared to MLK3 intact TAC littermates, indicating overt heart failure. Conclusion: (1) MLK3 functions as a tonic inhibitor of LV dysfunction and pathological remodeling through a role in the CM, possibly through sex-specific mechanisms. (2) Intact MLK3 is required for normal LV compensation and concentric remodeling in response to pressure overload. These findings have important clinical implications, as drugs which activate PKG1 in heart failure improve outcomes but are limited by excess hypotension. As a myocardial PKG1 substrate which opposes pathological LV remodeling through blood pressure-independent mechanisms, MLK3 may represent a candidate therapeutic target for heart failure. NIH 1R01HL162919. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

LEFT VENTRICULAR GEOMETRIC PATTERNS AND TRIGLYCERIDE–GLUCOSE (TYG) INDEX

Objective: Background and aim of the study: the triglyceride–glucose (TyG) index, an indirect index of insulin resistance, has been found associated to the development of heart failure (HF). Left ventricular hypertrophy and concentric geometry are associated to the future risk of cardiovascular events, including heart failure Design and method: In 1070 patients undergoing an echocardiogram and laboratory examinations at an ESH Excellence Centre for workup for suspect arterial hypertension (age 56±14 years, 49% males, 75% hypertensives (HT), among them 79% treated) left ventricular mass (LVM) and geometry were assessed. Subjects were divided into 4 LV geometric patterns according to the presence of an increased LV mass index (LVM/h2.7> 47 for females and and > 50 for males) and/or an increased relative wall thickness (RWT> 0.42). Results: After echocardiography subjects were classified as follows: 795(74%) with normal LV geometry (NG), 88 (8%) with concentric remodelling (CR), 143(13%) with eccentric hypertrophy (E_LVH) and 44 (4%) with concentric hypertrophy (C_LVH). The TyG was greater in males, in obese and in diabetic patients, and was significantly correlated with age, BMI, eGFR, systolic and diastolic blood pressure, LVM, LVMI and relative wall thickness. TyG remained significantly greater in patients with C_LVH as compared to both patients with NG and to patients with E_LVH, even after adjusting for multiple possible confounders (TyG: 8.5±0.6, 8.9±0.5, 8.6±0.6 and 9.0±0.7 and in patients with NG, CR, EH and CH respectively, ANOVA p < 0.05). The results did not change after excluding diabetic patients Conclusions: Conclusion: the triglyceride–glucose (TyG) index, an indirect index of insulin resistance is significantly associated to concentric LVH, independently of several possible confounders. These findings can explain at least in part the association between TyG and the risk of cardiovascular events.

Noninvasive measurement of tracer extraction efficiency in tissue, illustrated with Tc-99m-MAG3.

The aim of this study is to develop a noninvasive technique for measuring tissue tracer extraction efficiency ( E ) and illustrate it for Tc-99m-mercaptoacetyltriglycine (MAG3) and kidney. E was measured in 10 patients with normal MAG3 renography. E is the ratio of tissue clearance-to-blood flow ( Ki/F ). For single-photon tracers, attenuation constants are unknown, so Ki and F cannot be separately measured. However, by deriving attenuation-uncorrected Ki' and F' from the same regions of interests (ROIs), these constants cancel out, giving E . Using a lung ROI for blood activity, F was measured from first-pass and Ki' from Gjedde-Patlak-Rutland (GPR) analysis up to 130 s. Because of interference from right ventricle, a left ventricular ROI (LV) is unsuitable for F' but was used in GPR analysis, making an adjustment for the ratio of respective blood pool signals arising from lung and LV ROIs in early frames (60-90 s). A lung ROI underestimates F' by 4% at normal LV function. Chest wall interstitial activity ( I ), which does not affect F' , amounted to 53 and 30% of the lung and LV signals at 20 min, and 12 and 6% at 130 s, resulting in underestimations of Ki of 4 and 2%, respectively. Ignoring these opposing errors, E based on lung ROI for left and right kidneys was 43.5 (SD 8)% and 47.3 (9)%, and based on LV ROI for GPR analysis was 44.5 (10.9)% and 48.3 (10.6)%. E can be measured by combining blood flow from first-pass with clearance from GPR analysis, and has potential value both clinically and in clinical research.

Congenital Diaphragmatic Hernia Patients with Left Heart Hypoplasia and Left Ventricular Dysfunction Have Highest Odds of Mortality

To describe the scope of left ventricular (LV) dysfunction and left heart hypoplasia (LHH) in infants with congenital diaphragmatic hernia (CDH), to determine associations with CDH severity, and to evaluate the odds of extracorporeal membrane oxygenation (ECMO) and death with categories of left heart disease. Demographic and clinical variables were collected from a single-center, retrospective cohort of patients with CDH from January 2017 through May 2022. Quantitative measures of LV function and LHH were prospectively performed on initial echocardiograms. LHH was defined as ≥2 of the following: z score≤-2 of any left heart structure or LV end-diastolic volume <3mL. LV dysfunction was defined as shortening fraction <28%, ejection fraction <60%, or global longitudinal strain <20%. The exposure was operationalized as a 4-group categorical variable (LV dysfunction +/-, LHH +/-). Logistic regression models evaluated associations with ECMO and death, adjusting for CDH severity. One hundred eight-two patients (80.8% left CDH, 63.2% liver herniation, 23.6% ECMO, 12.1% mortality) were included. Twenty percent demonstrated normal LV function and no LHH (LV dysfunction-/LHH-), 37% normal LV function with LHH (LV dysfunction-/LHH+), 14% LV dysfunction without LHH (LV dysfunction+/LHH-), and 28% both LV dysfunction and LHH (LV dysfunction+/LHH+). There was a dose-response effect between increasing severity of left heart disease, ECMO use, and mortality. LV dysfunction+/LHH+infants had the highest odds of ECMO use and death, after adjustment for CDH severity [OR (95% CI); 1.76 (1.20, 2.62) for ECMO, 2.76 (1.63, 5.17) for death]. In our large single-center cohort, patients with CDH with LV dysfunction+/LHH+had the highest risk of ECMO use and death.

Biventricular performance in adults with a systemic right ventricle: new insights from myocardial work analysis.

To evaluate biventricular mechanics by means of echo-derived myocardial work (MW) analysis in patients with a systemic right ventricle (sRV). Comprehensive echo data were collected in all patients with a sRV who underwent transthoracic echocardiography at our tertiary centre between 2020 and 2021 including sRV function indices, global longitudinal strain (GLS) of right and left ventricle (RV/LV), biventricular MW, and atrial strain in those with congenitally corrected transposition of the great arteries (ccTGA). Fifty-six patients (37 [30.97-45.87]years, 59% male) and 49 healthy individuals matched per age and sex were included for comparison. Global work index (GWI:1106 [869.80-1293.10] Vs 314.2 [281.5-358.2]mmHg%,p < 0.0001) and global constructive work(GCW: 1542.50 [1338.9-1718.50] Vs 416.4 [365.70-464]mmHg%,p < 0.0001) were both increased for sRV compared to normal RV, reflecting exposition to a systemic afterload, with a contemporary raise in wasted work (GWW:197 [138.50-322.20] Vs 26.09 [17.80-43.48]mmHg%,p < 0.0001) and impaired efficiency (GWE:89 [83-93.54] Vs 93.67 [91.67-96] %,p < 0.0001). Conversely, sRV showed reduced MW indices in comparison to normal LV(p < 0.0001 for all). Non-systemic LV demonstrated normal GLS values (19.51 ± 3.9%), but reduced GWI (479 [368-665] Vs 2172 [1978-2386]mmHg%,p < 0.0001) and GCW (708 [490-815]mmHg% Vs 86.5 [59.25-118],p < 0.0001). Nevertherless, non-systemic LV showed also impaired efficiency (91 [88-94] Vs 95 [94-97]%,p < 0.0001). LVGLS values were related to RVGLS (R = 0.5,p = 0.00019), suggesting a consistent interventricular dependency. Atrial strain could be assessed in 16 out of 20 (80%) patients with ccTGA: both atria had reduced strain values compared to their normal counterparts. Moreover, pulmonary atrial strain during the reservoir phase was related to LVGWE (R = 0.58,p = 0.047) and inversely related to LVGLS (R=-0.71,p = 0.0043). MW analysis is feasible in sRV and may provide additional clinical data. In our cohort MW revealed biventricular impairment, in particular for non-systemic LV, in spite of normal GLS values.

Left Ventricular Mass, Geometric Patterns, and Diastolic Myocardial Performance in Children with Obstructive Sleep Apnea

Background: Obstructive sleep apnea (OSA), characterized by recurrent partial or complete upper airway obstructions during sleep, is an established risk factor for cardiovascular diseases in children. This study aims to determine the prevalence of left ventricular hypertrophy (LVH), abnormal left ventricular (LV) geometric patterns, and diastolic dysfunction in children with OSA and compare them with healthy controls. Materials and Methods: This was a cross-sectional comparative study conducted on 75 eligible children with OSA aged 2–14 years and 75 age- and sex-matched healthy children. Transthoracic echocardiography was used to assess the LV structures and diastolic function in all the subjects. Results: The mean LV mass index was significantly higher in the patients with OSA (36.53 ± 9.1 g/m2.7) as compared to the control group (32.82 ± 7.9 g/m2.7) (P = 0.008), and it showed a significant correlation with decreasing peripheral oxygen saturation (r = −0.35, P = 0.002). LVH was present in 8.0% of the patients with OSA and none (0%) of the controls. 29.3% of the patients with OSA and 1.3% of the healthy controls had abnormal LV geometry. LV diastolic dysfunction was present in 6.7% of the patients with OSA and 0% of the controls. LV diastolic dysfunction was significantly higher among the patients with OSA who have abnormal LV geometry compared to those with normal LV geometry (P = 0.002). Conclusion: LVH, abnormal LV geometry, and diastolic dysfunction are more common in children with OSA than in healthy controls. Children with OSA and abnormal LV geometry are more likely to have LV diastolic dysfunction.

Unveiling Cardiac Involvement in Juvenile Dermatomyositis Through Speckle-Tracking Echocardiography.

Early detection of cardiac involvement in Juvenile Dermatomyositis (JDM) is difficult due to the absence of clinical signs and symptoms, with systolic dysfunction often emerging in late stages and associated with a poor prognosis. This study aimed to employ two-dimensional speckle-tracking echocardiography (STE) for subclinical assessment of left ventricular (LV) systolic failure in JDM and explore potential associations between impaired LV systolic function (LV-GLS) and disease activity. A prospective study enrolled 20 healthy volunteers and 26 JDM patients (< 18years old) without cardiac symptoms. Clinical data were collected from medical records, and echocardiograms were conducted by a pediatric cardiologist. Our study cohort demonstrated similar age to controls (13.5 ± .6 vs. 13.8 ± 4.7; p = 0.465). Median illness duration at echocardiography was 5 (1.5-17.5) years, and conventional echocardiography indicated normal LV ejection fraction (> 55%) in all participants. However, STE revealed lowered LV GLS in JDM patients (-22.2 ± 4.1% vs. -26.5 ± 5.3% p = 0.022). Pulse steroid users displayed lower GLS average values compared to non-users (β = 4.99, 95% CI 1.34-8.64, p = 0.009). Negative correlations existed between LV-GLS and age at diagnosis (r = -0.499; p = 0.011), diastolic parameters (E/E' ratio) and age at diagnosis (r = -0.469; p = 0.018), as well as RV global strain and age at diagnosis (r = -0.443; p = 0.024). Employing STE in JDM patients facilitated the identification of preclinical cardiac dysfunction. Given JDM patients' younger age, early myocardial damage detection through STE may impact treatment decisions and long-term cardiovascular prognosis.

Cardiac magnetic resonance patterns of left ventricular remodeling in patients with severe aortic stenosis referred to surgical aortic valve replacement

Left ventricular (LV) hypertrophy is a common finding in patients with severe aortic stenosis (AS). Cardiac magnetic resonance (CMR) is the gold-standard technique to evaluate LV remodeling. Our aim was to assess the prevalence and describe the patterns of LV adaptation in AS patients before and after surgical aortic valve replacement (AVR). Prospective study of 130 consecutive patients (71y [IQR 68–77y], 48% men) with severe AS, referred for surgical AVR. Patterns of LV remodeling were assessed by CMR. Besides normal LV ventricular structure, four other patterns were considered: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, and adverse remodeling. At baseline CMR study: mean LV indexed mass: 81.8 ± 26.7 g/m2; mean end-diastolic LV indexed volume: 85.7 ± 23.1 mL/m2 and median geometric remodeling ratio: 0.96 g/mL [IQR 0.82–1.08 g/mL]. LV hypertrophy occurred in 49% of subjects (concentric 44%; eccentric 5%). Both normal LV structure and concentric remodeling had a prevalence of 25% among the cohort; one patient had an adverse remodeling pattern. Asymmetric LV wall thickening was present in 55% of the patients, with predominant septal involvement. AVR was performed in 119 patients. At 3–6 months after AVR, LV remodeling changed to: normal ventricular geometry in 60%, concentric remodeling in 27%, concentric hypertrophy in 10%, eccentric hypertrophy in 3% and adverse remodeling (one patient). Indexes of AS severity, LV systolic and diastolic function and NT-proBNP were significantly different among the distinct patterns of remodeling. Several distinct patterns of LV remodelling beyond concentric hypertrophy occur in patients with classical severe AS. Asymmetric hypertrophy is a common finding and LV response after AVR is diverse.

Myocardial deformation characteristics assessed by cardiovascular magnetic resonance feature tracking in a healthy Chinese population

PurposeTo explore global/regional myocardial deformation across various layers, vascular distributions, specific levels and distinct walls in healthy individuals using cardiovascular magnetic resonance feature tracking (CMR-FT). MethodsWe selected a cohort of 55 healthy participants and CMR cine images were used to obtain the left ventricular (LV) peak longitudinal, circumferential, radial strains (LS, CS, RS). The characteristics of normal LV strain in various layers (endocardium, myocardium, epicardium), territories [left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA)], levels (basal, middle, apical) and walls (anterior, septum, inferior, lateral) were compared. ResultsThe absolute values of the LV global LS and CS gradually decreased from endocardium to epicardium. The absolute LV global RS (65.7 ± 47.7%) was maximum relative to LS (−22.0 ± 10.8%) and CS (−22.8 ± 7.7%). The absolute values of the LCX territorial strain were the largest compared with the LAD and RCA territorial strains. Regional RS, endo-CS and endo-LS gradually increased from the basal to the apical level. The LV lateral walls had the highest strain values (CS, LS, and RS). ConclusionsVariations in normal LV strain values across various layers, territories, levels, and walls were observed, suggesting the necessity for careful clinical interpretation of these strain values. These findings also partially revealed the complexity of normal cardiac mechanics.

Shock indices are associated with in-hospital mortality among patients with septic shock and normal left ventricular ejection fraction.

The understanding of shock indices in patients with septic shock is limited, and their values may vary depending on cardiac function. This prospective cohort study was conducted across 20 university-affiliated hospitals (21 intensive care units [ICUs]). Adult patients (≥19 years) with septic shock admitted to the ICUs during a 29-month period were included. The shock index (SI), diastolic shock index (DSI), modified shock index (MSI), and age shock index (Age-SI) were calculated at sepsis recognition (time zero) and ICU admission. Left ventricular (LV) function was categorized as either normal LV ejection fraction (LVEF ≥ 50%) or decreased LVEF (<50%). Among the 1,194 patients with septic shock, 392 (32.8%) who underwent echocardiography within 24 h of time zero were included in the final analysis (normal LVEF: n = 246; decreased LVEF: n = 146). In patients with normal LVEF, only survivors demonstrated significant improvement in SI, DSI, MSI, and Age-SI values from time zero to ICU admission; however, no notable improvements were found in all patients with decreased LVEF. The completion of vasopressor or fluid bundle components was significantly associated with improved indices in patients with normal LVEF, but not in those with decreased LVEF. In multivariable analysis, each of the four indices at ICU admission was significantly associated with in-hospital mortality (P < 0.05) among patients with normal LVEF; however, discrimination power was better in the indices for patients with lower lactate levels (≤ 4.0 mmol/L), compared to those with higher lactate levels. The SI, DSI, MSI, and Age-SI at ICU admission were significantly associated with in-hospital mortality in patients with septic shock and normal LVEF, which was not found in those with decreased LVEF. Our study emphasizes the importance of interpreting shock indices in the context of LV function in septic shock.

Cardiac biopsies reveal differences in transcriptomics between left and right ventricle in patients with or without diagnostic signs of heart failure

New or mild heart failure (HF) is mainly caused by left ventricular dysfunction. We hypothesised that gene expression differ between the left (LV) and right ventricle (RV) and secondly by type of LV dysfunction. We compared gene expression through myocardial biopsies from LV and RV of patients undergoing elective coronary bypass surgery (CABG). Patients were categorised based on LV ejection fraction (EF), diastolic function and NT-proBNP into pEF (preserved; LVEF ≥ 45%), rEF (reduced; LVEF < 45%) or normal LV function. Principal component analysis of gene expression displayed two clusters corresponding to LV and RV. Up-regulated genes in LV included natriuretic peptides NPPA and NPPB, transcription factors/coactivators STAT4 and VGLL2, ion channel related HCN2 and LRRC38 associated with cardiac muscle contraction, cytoskeleton, and cellular component movement. Patients with pEF phenotype versus normal differed in gene expression predominantly in LV, supporting that diastolic dysfunction and structural changes reflect early LV disease in pEF. DKK2 was overexpressed in LV of HFpEF phenotype, potentially leading to lower expression levels of β-catenin, α-SMA (smooth muscle actin), and enhanced apoptosis, and could be a possible factor in the development of HFpEF. CXCL14 was down-regulated in both pEF and rEF, and may play a role to promote development of HF.

Takotsubo syndrome after bilateral simultaneous total knee arthroplasty - A case report

IntroductionCardiac complications represents a major cause of morbidity and mortality especially after bilateral simultaneous total knee arthroplasty (BS-TKA). Takotsubo syndrome after BS-TKA has not been described in the literature. Case presentationA 60 years-old women underwent BS- TKA and she suddenly developed bradycardia and hypotension after second knee wound closure. The electrocardiography revealed ST elevation and echocardiography showed apical hypokinesia of left ventricle. Coronary angiography revealed normal epicardial coronaries and a provisional diagnosis of Takotsubo cardiomyopathy was made. Serial ECGs revealed resolution of ST elevation and normal LV function within 5 days. On one-year follow up, she was able to do all her normal activities, and 12-lead electrocardiography were back to normal. ConclusionCardiac complications represents a major cause of morbidity and mortality especially after BS-TKA. Surgeons must be vigilant in the postoperative period for any likely precipitating factors of stress induced cardiomyopathy. Takotsubo syndrome should be considered as a differential diagnosis with features of acute coronary syndrome in elderly post-menopausal patients.

Two-dimensional speckle tracking echocardiography in chemotherapy-induced cardiotoxicity in females with breast cancer

BackgroundCancer and cardiovascular diseases are the main causes of mortality worldwide. Although the incidence of cancer is rising, modern comprehensive management including surgery, chemotherapy, and radiotherapy led to decreased mortality, but also different cardiovascular complications. Conventional EF measurement fails to detect subtle changes in LV function, so a more sensitive tool is needed.MethodsThe study included 101 asymptomatic female patients with newly diagnosed breast cancer who received anthracycline ± trastuzumab-based chemotherapy regimen. A comprehensive echocardiographic examination was performed before receiving the chemotherapy (T0), at 3 months (T1), and at 6 months after (T2). All patients had pre-treatment normal LV EF. Asymptomatic CTRCD is defined as: severe if new LVEF reduction to < 40%, moderate if new LVEF reduction by ≥ 10 percentage points to an LVEF of 40–49% or new LVEF reduction by, 10 percentage points to an LVEF of 40– 49% and either new relative decline in GLS by .15% from baseline or new rise in cardiac biomarkers and mild if LVEF ≥ 50% and new relative decline in GLS by .15% from baseline and/or new rise in cardiac biomarkers. Symptomatic CTRCD is defined as: very severe if HF requiring inotropic support, mechanical circulatory support, or consideration of transplantation, severe if required hospitalization, moderate if required outpatient intensification of diuretic and HF therapy and mild if there are mild HF symptoms and no intensification of therapy required according to the latest ESC cardio oncology guidelines. The Lower reference value set for RV S’ was less than 10cm/s to define RV systolic dysfunction according to ASE guidelines.ResultsCTRCD occurred in 24 patients (25.5%) while RV systolic dysfunction was more common occurring in 37 patients (39.4%). LV GLS at (T1) (cut-off value < -15% with relative 12.5% reduction from the baseline value) was a strong predictor of CTRCD, but combining LV GLS with RV GLS & RV FWLS was the strongest (AUC = 0.947, sensitivity = 91.67%, specificity = 90%).ConclusionChemotherapy induces biventricular changes with more prevalent deterioration in RV values. Low LV & RV strain values at baseline together with reduction of these values after chemotherapy treatment can predict later CTRCD development. Combining LV GLS with RV GLS & FWLS values at (T1) is the strongest predictor of subsequent CTRCD.

Prognostic value of visual and quantitative CMR regional myocardial function in patients with suspected myocarditis

According to updated Lake-Louise Criteria, impaired regional myocardial function serves as a supportive criterion in diagnosing myocarditis. This study aimed to assess visual regional wall motional abnormalities (RWMA) and novel quantitative regional longitudinal peak strain (RLS) for risk stratification in the clinical setting of myocarditis. In patients undergoing CMR and meeting clinical criteria for suspected myocarditis global longitudinal strain (GLS), late gadolinium enhancement (LGE), RWMA and RLS were assessed in the anterior, septal, inferior, and lateral regions and correlated to the occurrence of major adverse cardiac events (MACE), including heart failure hospitalization, sustained ventricular tachycardia, recurrent myocarditis, and all-cause death. In 690 consecutive patients (age: 48.0 ± 16.0 years; 37.7% female) with suspected myocarditis impaired RLS was correlated with RWMA and LV-GLS but not with the presence of LGE. At median follow up of 3.8 years, MACE occurred in 116 (16.8%) patients. Both, RWMA and RLS in anterior-, septal-, inferior-, and lateral- locations were univariately associated with outcomes (all p < 0.001), but not after adjusting for clinical characteristics and LV-GLS. In the subgroup of patients with normal LV function, RWMA were not predictive of outcomes, whereas septal RLS had incremental and independent prognostic value over clinical characteristics (HRadjusted = 1.132, 95% CI 1.020–1.256; p = 0.020). RWMA and RLS can be used to assess regional impairment of myocardial function in myocarditis but are of limited prognostic value in the overall population. However, in the subgroup of patients with normal LV function, septal RLS represents a distinctive marker of regional LV dysfunction, offering potential for risk-stratification.Graphical abstractCI: confidence interval, CMR: cardiac magnetic resonance imaging, HR: hazard ratio, MACE major adverse cardiovascular events

Do False Tendons Prevent Adverse Left Ventricular Remodeling After Anterior Wall Myocardial Infarction? An Echocardiographic Strain Imaging Study

The role of muscular left ventricular (LV) false tendons (FTs) is poorly understood. To gain insight into their pathophysiologic significance, we adapted echocardiographic LV strain imaging software to measure LVFT longitudinal strain in subjects with normal left ventricles and in patients who sustained previous anterior wall myocardial infarction (AWMI). GE EchoPAC software was used to measure longitudinal strain in LVFTs ≥0.3 cm in diameter. Tendinous strain was measured in 11 patients with LVFTs confined to the left anterior descending artery territory (connecting the anteroseptum or anterior wall to the apex) ≥6 months after AWMI (myocardial infarction [MI]+FT+ group) and in 25 patients with normal hearts containing LVFTs (MI-FT+ group). We also compared the indexed LV end-diastolic volumes in the MI+FT+ group to that of 25 patients with previous AWMI without LVFTs (MI+FT- group). The mean LVFT strain in MI+FT+ group was 5.5 ± 6.2% and -28.9 ± 4.7% in the MI-FT+ group (p <0.0001). The indexed LV end-diastolic volume in the MI+FT+ group did not differ from the MI+FT- group (88.4 ± 17.8 vs 87.9 ± 17 ml/m2, p = 0.90). In conclusion, the negative strain (contraction) developed by LVFTs in the MI-FT+ group may help maintain normal LV size and shape by generating inward restraining forces. The development of positive strain (stretch) in LVFTs in patients in the MI+FT+ group suggests they become infarcted after AWMI. This implies that they are incapable of generating inward restraining forces that might otherwise mitigate adverse remodeling. Of note, LV volumes after AWMI do not differ whether or not LVFTs are present.

Noninvasive Prediction of Pulmonary Capillary Wedge Pressure in Patients With Normal Left Ventricular Ejection Fraction: Comparison of Cardiac Magnetic Resonance With Comprehensive Echocardiography

Cardiac magnetic resonance (CMR) was recently reported to predict mean pulmonary capillary wedge pressure (PCWP). However, there is a paucity of data on its accuracy for estimation of PCWP in patients with normal left ventricular (LV) ejection fraction (EF). We sought to examine its accuracy against the invasive gold standard and to compare it with the accuracy of comprehensive echocardiography. Stable patients with EF of ≥50% who underwent right heart catheterization, CMR, and echocardiographic imaging within 1week were included. Pulmonary capillary wedge pressure was estimated by CMR using a previously validated equation where PCWP is estimated based on the left atrial maximum volume and LV mass. Echocardiographic estimation of PCWP was based on 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines, taking into account the presence of myocardial disease. The mean age of the 79 patients was 55±15years, and 58.2% were female. There were 33 patients with PCWP >15mm Hg by right heart catheterization. Cardiac magnetic resonance prediction of PCWP had an area under the curve (AUC)=0.72. In comparison, echocardiographic prediction of PCWP showed a higher accuracy (AUC=0.87 vs AUC=0.72; P=.008). In patients with normal LV EF, CMR estimation of mean PCWP based on LV mass and left atrial volume has modest accuracy for detecting patients with mean PCWP >15mm Hg. Comprehensive echocardiography predicts elevated PCWP with higher accuracy in comparison with CMR.

Results of the Double Switch Operation in Patients Who Previously Underwent Left Ventricular Retraining.

Congenitally corrected transposition of the great arteries (CC-TGA) is a complex form of congenital heart disease that has numerous subtypes. While most patients with CC-TGA have a large ventricular septal defect (VSD) and pulmonary stenosis, there are some patients who have either no VSD or a highly restrictive VSD. These patients will require left ventricular (LV) retraining prior to double switch. The purpose of this study was to review our experience with the double switch procedure in patients who had previously undergone LV retraining. This was a retrospective review of a single institution experience with the double switch procedure in patients who had undergone LV retraining (2002-present). Forty-five patients underwent double switch following LV retraining. Of these, 39 had an arterial switch with hemi-Mustard/bidirectional Glenn and six had a Senning. The median cross-clamp time was 135 min (range 71-272) and median bypass time was 202 min (range 140-430 min). Median hospital length of stay was eight days (range 4-108). There were no in-hospital deaths. Median duration of follow-up was 30 months (range 0-175). One patient subsequently underwent heart transplantation and died 65 months following double switch. At follow-up, 41 of the 44 survivors (93%) have normal or low normal LV function and 40 of the 44 survivors (91%) have no or trace mitral regurgitation. The data demonstrate early and mid-term survival of 100% and 97%. Ninety-three percent had preserved LV function. These results suggest that patients with CC-TGA who undergo LV retraining and double switch can have excellent clinical outcomes.

The association of plasma connective tissue growth factor levels with left ventricular diastolic dysfunction in patients with overt hyperthyroidism.

Left ventricular (LV) diastolic dysfunction is an independent predictor of future cardiovascular events. Early detection of patients with LV diastolic dysfunction can improve clinical outcomes through active management. However, the assessment of diastolic function is very complicated, and there are currently lack of effective biomarkers to assess the risk of LV diastolic dysfunction. Connective tissue growth factor (CTGF) plays a significant role in cardiac remodeling and dysfunction. We aimed to investigate the associations between plasma CTGF level and the risk of LV diastolic dysfunction in this study and judge its effectiveness in diagnosing LV diastolic dysfunction. A total of 169 patients with overt hyperthyroidism were included. LV diastolic function was evaluated and the subjects were divided into normal LV diastolic function group and LV diastolic dysfunction group. Routine clinical medical data, biochemical data, thyroid related parameters and echocardiographic parameters were recorded for analysis. Compared with normal LV diastolic function group, the LV diastolic dysfunction group had higher age and BMI, as well as lower heart rate, lower serum albumin, lower eGFR, higher serum TgAb and BNP level, and the incidences of hypertension were also higher (all P <0.05). Circulating plasma CTGF levels in the LV diastolic dysfunction group were significantly higher (normal LV diastolic function group: 7.026 [5.567-8.895], LV diastolic dysfunction group: 8.290 [7.054-9.225] ng/ml, median [(Interquartile range)], P = 0.004); Compared with the lowest quartile group, the crude odds ratios (OR) of LV diastolic dysfunction in the second, third, and fourth quartile group were 3.207, 5.032 and 4.554, respectively (all P<0.05). After adjustment for the potentially confounding variables, the adjusted OR values of the third and fourth quartile group had no obvious change. The results of ROC showed that the plasma CTGF had the largest area under the ROC curve, and the value was 0.659 (P = 0.005). The level of circulating plasma CTGF in the LV diastolic dysfunction group was significantly increased. Plasma CTGF level is an independent risk factor for LV diastolic dysfunction. Compared with serum BNP level, the plasma CTGF level may have auxiliary diagnostic value for LV diastolic dysfunction in hyperthyroid patients.

Prevalence and prognosis of hyperdynamic left ventricular systolic function in septic patients: a systematic review and meta-analysis

PurposeThe prevalence of hyperdynamic left ventricular (LV) systolic function in septic patients and its impact on mortality remain controversial. In this systematic review and meta-analysis, we investigated the prevalence and association of hyperdynamic LV systolic function with mortality in patients with sepsis.MethodsWe searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Primary outcomes were the prevalence of hyperdynamic LV systolic function in adult septic patients and the associated short-term mortality as compared to normal LV systolic function. Hyperdynamic LV systolic function was defined using LV ejection fraction (LVEF) of 70% as cutoff. Secondary outcomes were heart rate, LV end-diastolic diameter (LVEDD), and E/e’ ratio.ResultsFour studies were included, and the pooled prevalence of hyperdynamic LV systolic function was 18.2% ([95% confidence interval (CI) 12.5, 25.8]; I2 = 7.0%, P < 0.0001). Hyperdynamic LV systolic function was associated with higher mortality: odds ratio of 2.37 [95%CI 1.47, 3.80]; I2 = 79%, P < 0.01. No difference was found in E/e’ (P = 0.43) between normal and hyperdynamic LV systolic function, while higher values of heart rate (mean difference: 6.14 beats/min [95%CI 3.59, 8.69]; I2 = 51%, P < 0.0001) and LVEDD (mean difference: − 0.21 cm [95%CI − 0.33, − 0.09]; I2 = 73%, P < 0.001) were detected in patients with hyperdynamic LV systolic function.ConclusionThe prevalence of hyperdynamic LV systolic function is not negligible in septic patients. Such a finding is associated with significantly higher short-term mortality as compared to normal LV systolic function.

Association of global longitudinal strain by feature tracking cardiac magnetic resonance imaging with adverse outcomes among community-dwelling adults without cardiovascular disease: The Dallas Heart Study.

Left ventricular (LV) global longitudinal strain (GLS) may detect subtle abnormalities in myocardial contractility among individuals with normal LV ejection fraction (LVEF). However, the prognostic implications of GLS among healthy, community-dwelling adults is not well-established. Overall, 2234 community-dwelling adults (56% women, 47% Black) with LVEF ≥50% without a history of cardiovascular disease (CVD) from the Dallas Heart Study who underwent cardiac magnetic resonance (CMR) with GLS assessed by feature tracking CMR (FT-CMR) were included. The association of GLS with the risk of incident major adverse cardiovascular events (MACE; composite of incident myocardial infarction, incident heart failure [HF], hospitalization for atrial fibrillation, coronary revascularization, and all-cause death), and incident HF or death were assessed with adjusted Cox proportional hazards models. A total of 309 participants (13.8%) had MACE during a median follow-up duration of 17 years. Participants with the worst GLS (Q4) were more likely male and of the Black race with a history of tobacco use and diabetes with lower LVEF, higher LV end-diastolic volume, and higher LV mass index. Cumulative incidence of MACE was higher among participants with worse (Q4 vs. Q1) GLS (20.4% vs. 9.0%). In multivariable-adjusted Cox models that included clinical characteristics, cardiac biomarkers and baseline LVEF, worse GLS (Q4 vs. Q1) was associated with a significantly higher risk of MACE (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.07-2.24, p = 0.02) and incident HF or death (HR 1.57, 95% CI 1.03-2.38, p = 0.04). Impaired LV GLS assessed by FT-CMR among adults free of cardiovascular disease is associated with a higher risk of incident MACE and incident HF or death independent of cardiovascular risk factors, cardiac biomarkers and LVEF.