Decline In Left Ventricular Function Research Articles

Impact of systolic coronary flow reversal in patients with aortic stenosis: assessment with transthoracic echocardiography

Abstract Background In patients with aortic stenosis (AS), increased systolic wall stress due to increased afterload reduces systolic coronary flow, often leading to systolic coronary flow reversal (SFR) in epicardial coronary arteries. Purpose We used transthoracic echocardiography (TTE) to evaluate severity of AS, left ventricular function, and coronary flow, and investigated echocardiographic indicators associated with SFR. Methods We prospectively evaluated consecutively presenting patients who visited our valvular heart disease outpatient clinic or were admitted to our hospital for investigation of AS (July 2023 to February 2024). Based on ESC guidelines, severity of AS and the left ventricular function were assessed with TTE. At the same time, TTE was used to measure distal left anterior descending coronary artery flow. SFR was defined as the presence of a reversal coronary flow component in systole. Based on the presence or absence of SFR in coronary flow measurements, patients were classified into SFR+ or SFR− groups. The inclusion criteria were AS of moderate or greater severity, and the exclusion criteria were known coronary stenosis and the inability to assess coronary flow. Results Enrolled 28 patients were classified into SFR+ (7 patients) and SFR − (21 patients) groups. Comparing baseline characteristics between the SFR+ and SFR− groups, although there were no significant differences in left ventricular indicators such as left ventricular mass index, left ventricular ejection fraction, stroke volume index, and E/e’ between the two groups, left ventricular global longitudinal strain was significantly lower in the SFR+ group (12.0±3.1%, 14.9±3.0%, p=0.026) (Table 1). Regarding indexes of AS assessment, aortic valve peak velocity and aortic valve mean pressure gradient values were significantly higher in the SFR+ group than in the SFR − group ([475±68 cm/s, 379±55 cm/s, p<0.001] and [56.2±16.5 mm Hg, 34.8±10.5 mm Hg, p<0.001], respectively) (Table 1). Representative cases show Figure 1. Conclusion The presence of SFR in patients with AS assessed using TTE may be a simple echocardiographic index that may be associated with potential decline in left ventricular function and progression of AS.

NT-proBNP and Cardiac Troponin I, but Not Cardiac Troponin T, Are Associated With 7-Year Changes in Cardiac Structure and Function in Older Adults: The ARIC Study.

Higher circulating concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are associated with left ventricular remodeling and with incident heart failure. The associations of these cardiac biomarkers with changes in cardiac structure and function over time are uncharacterized. Among 2006 participants in the ARIC prospective cohort study (Atherosclerosis Risk in Communities) who were free of overt cardiovascular disease and underwent echocardiography at study visits 5 (2011- 2013) and 7 (2018-2019), we assessed the associations of NT-proBNP, hs-cTnT, and hs-cTnI concentrations at visit 5 with changes in left ventricular structure and function between visits 5 and 7 (≈7-year change) using multivariable linear regression with the biomarkers modeled as restricted cubic splines. Models were adjusted for age, sex, race, body mass index, smoking, diabetes, hypertension, and renal function at visit 5; blood pressure and heart rate at both visits; and the baseline value of the echocardiographic parameter of interest. Mean±SD age was 74±4 years at visit 5; 61% were women; and 23% were Black adults. Median (25th-75th percentile) concentrations at visit 5 of NT-proBNP, hs-cTnT, and hs-cTnI were 87 ng/L (50-157 ng/L), 9 ng/L (6-12 ng/L), and 2.6 ng/L (1.9-3.9 ng/L). In adjusted models, elevated baseline concentrations of NT-proBNP and hs-cTnI were significantly associated with 7-year decline in left ventricular systolic function (ejection fraction, longitudinal and circumferential strain) and worsening diastolic indices. In contrast, elevated baseline concentrations of hs-cTnT were not significantly associated with 7-year changes in cardiac structure, systolic function, or diastolic function (all P>0.05). Higher concentrations of NT-proBNP and hs-cTnI, but not hs-cTnT, were associated with greater declines in left ventricular function over ≈7 years in late life independently of traditional cardiovascular risk factors.AQ.

Anthracycline therapy induces an early decline of cardiac contractility in low-risk patients with breast cancer

AimsCancer therapy-related cardiac dysfunction (CTRCD) is a dreaded complication of anthracycline therapy. CTRCD most frequently appears in patients with cardiovascular risk factors (CVR) or known cardiovascular disease. However, limited data exist on incidence and course of anthracycline-induced CTRCD in patients without preexisting risk factors.We therefore aimed to longitudinally investigate a cohort of young women on anthracycline treatment due to breast cancer without cardiovascular risk factors or known cardiovascular disease (NCT03940625).Methods and resultsWe enrolled 59 women with primary breast cancer and scheduled anthracycline-based therapy, but without CVR or preexisting cardiovascular disease. We conducted a longitudinal assessment before, immediately and 12 months after cancer therapy with general laboratory, electrocardiograms, echocardiography and cardiovascular magnetic resonance (CMR), including myocardial relaxometry with T1, T2 and extracellular volume mapping.Every single patient experienced a drop in CMR-measured left ventricular ejection fraction (LVEF) of 6 ± 3% immediately after cancer therapy. According to the novel definition 32 patients (54.2%) developed CTRCD after 12 months defined by reduction in LVEF, global longitudinal strain (GLS) and/or biomarkers elevation, two of them were symptomatic. Global myocardial T2 relaxation times as well as myocardial mass increased coincidently with a decline in wall-thickening. While T2 values and myocardial mass normalized after 12 months, LVEF and GLS remained impaired.ConclusionIn every single patient anthracyclines induce a decline of myocardial contractility, even among patients without pre-existing risk factors for CTRCD. Our data suggest to thoroughly evaluate whether this may lead to an increased risk of future cardiovascular events.Graphical Reduced myocardial contractility in low-risk patients receiving anthracycline-based cancer therapy. This study included 59 otherwise healthy women with primary breast cancer undergoing anthracycline-based chemotherapy. CMR was performed at baseline, directly and 12 months after cancer therapy. A decline in left ventricular function was observed in every single patient accompanied by transient edema. More than 50% were diagnosed with cancer therapy related cardiovascular dysfunction. LVEF: left ventricular function, CTRCD: cancer therapy related cardiovascular dysfunction, GLS = Global longitudinal strain, hs-TnT= high sensitive Troponin T, NT-pro BNP = NT-pro brain natriuretic peptide

Impact of Functional Mitral Regurgitation on Left Ventricular Strain in Nonischemic Dilated Cardiomyopathy Patients with Type 2 Mellitus Diabetes: A Magnetic Resonance Feature Tracking Study

BackgroundThe impact of functional mitral regurgitation and type 2 mellitus diabetes (T2DM) on left ventricular (LV) strain in nonischemic dilated cardiomyopathy (NIDCM) patients remains unclear.PurposeTo evaluate the impact of mitral regurgitation severity on LV strain, and explore additive effect of T2DM on LV function across varying mitral regurgitation severity levels in NIDCM patients.Study TypeRetrospective.Population352 NIDCM (T2DM−) patients (49.1 ± 14.6 years, 67% male) (207, 85, and 60 no/mild, moderate, and severe mitral regurgitation) and 96 NIDCM (T2DM+) patients (55.2 ± 12.4 years, 77% male) (47, 30, and 19 no/mild, moderate, and severe mitral regurgitation).Field Strength/Sequence3.0 T/balanced steady‐state free precession sequence.AssessmentLV geometric parameters and strain were measured and compared among groups. Determinants of LV strain were investigated.Statistical TestStudent's t‐test, Mann–Whitney U test, one‐way ANOVA, Kruskal‐Wallis test, univariable and multivariable linear regression. P < 0.05 was considered statistically significant.ResultsLV GLPS and longitudinal PDSR decreased gradually with increasing mitral regurgitation severity in NIDCM patients with T2DM(GLPS: −5.7% ± 2.1% vs. −4.3% ± 1.6% vs. −2.6% ± 1.3%; longitudinal PDSR:0.5 ± 0.2 sec−1 vs. 0.4 ± 0.2 sec−1 vs. 0.3 ± 0.1 sec−1). NIDCM (T2DM+) demonstrated decreased GCPS and GLPS in the no/mild subgroup, reduced LV GCPS, GLPS, and longitudinal PDSR in the moderate subgroup, and reduced GRPS, GCPS, GLPS, and longitudinal PDSR in the severe subgroup compared with NIDCM (T2DM−) patients. Multivariable regression analysis identified that mitral regurgitation severity (β = −0.13, 0.15, and 0.25 for GRPS, GCPS, and GLPS) and the presence of T2DM (β = 0.14 and 0.13 for GCPS and GLPS) were independent determinants of LV strains in NIDCM patients.Data ConclusionIncreased mitral regurgitation severity is associated with reduced LV strains in NIDCM patients with T2DM. The presence of T2DM exacerbated the decline of LV function across various mitral regurgitation levels in NIDCM patients, resulting in reduced LV strains.Level of Evidence3.Technical EfficacyStage 3.

Right ventricular-pulmonary artery coupling in the early stages of infarction could optimize patient risk stratification over five years

Abstract Background Right ventricular (RV) dysfunction is recognized as a cardinal prognostic marker in heart failure (HF) patients. Myocardial infarction (MI) is often followed by unrecognized RV dysfunction, which can be associated with worse outcome. It is recently shown that the ratio between TAPSE and PASP (RV/PA) may depict cardiopulmonary hemodynamics better than the two parameters alone. Aim To evaluate the interactions between left ventricular (LV) and RV function in early phase of MI and to assess the prognostic significance of RV/PA coupling in patients with first MI during 5 years follow up. Methods The prospective study included 144 patients with the first MI treated with the primary percutaneous coronary intervention (p PCI) who underwent Doppler echocardiography within 2±1 days of MI. LV function analysis included: LV ejection fraction (EF), ratio between early diastolic velocity and tissue annular velocity (E/e) and global longitudinal strain (GLS). RV function and RV-PA interaction was expressed as ratio between TAPSE and PASP. During the five-year follow-up, major cardiovascular events and especially hospitalization for HF were analyzed. Results Progressive RV/PA uncoupling was associated with higher degree of LV impairment and dysfunction (EF p<0.001, E/e p=0.002, GLS p<0.001) and severity of mitral regurgitation (p=0.013). Lower baseline RV/PA coupling significantly reflects the frequency of hospitalizations for HF in the population of patients with first MI during five-year follow-up (0.62 v.s.0.51, p=0.021). After multivariate adjustment RV/PA remained an independent predictor of all major cardiac events (MACE) after five years (OR 14.0 [1.5–130.8], p=0.019). Conclusion A lower baseline RV-PA coupling, reflecting a higher degree of LV-induced pulmonary hypertension and secondary RV-dysfunction, is associated with decline of LV function in early phase of MI, and is independently associated with worse prognosis after five years. The value of RV-PA ratio as an prognstic marker warrants further investigation.

Impact of atrial fibrillation burden on longitudinal changes in left ventricular structure and function: a post-hoc analysis of a randomized clinical trial

Abstract Background Atrial fibrillation (AF) is a well-established risk factor for heart failure (HF), stroke, and left ventricular (LV) dysfunction. However, only limited longitudinal data exist regarding the impact of AF burden on left ventricular (LV) structure and function. Purpose The aim of this study was to investigate the association between AF burden and longitudinal changes in LV structure and function in an older patient population with cardiac risk factors. Methods This study was a post-hoc analysis of a randomized clinical trial, which investigated whether AF screening with implantable loop recorders (ILRs) and subsequent initiation of anticoagulation could prevent stroke in high-risk individuals. As a substudy, a group of participants had extensive transthoracic echocardiography performed at baseline and a re-examination after ILR end-of-life. We included participants with available ILR data and echocardiographic data from both baseline and follow-up. We excluded participants with ongoing AF during the baseline echocardiogram. AF episodes were adjudicated by two cardiologists and AF burden was calculated as the percentage of time spent in AF during the total ILR monitoring period. Univariable and multivariable linear regression models were used to investigate the association between AF burden and changes in echocardiographic measures. The multivariable model was adjusted for age, sex, systolic blood pressure, diabetes, smoking status, previously acute myocardial infarction, previous coronary artery bypass grafting, prevalent HF, body mass index, estimated glomerular filtration rate, number of days monitored by ILR, and the number of days between the two echocardiographic examinations. Both models included adjustment for the baseline value of the echocardiographic measure. Results The study population consisted of 640 participants with available baseline and follow-up echocardiograms. Mean age was 73.6 years (±3.4 years) and 278 (43.4%) were women. AF was documented in 188 (29.4%) participants during a median ILR monitoring period of 3.2 years (IQR 2.9-3.4 years). The mean timespan between the echocardiographic examinations was median 5.0 (IQR 4.6-5.2) years. Among participants with AF, the median AF burden was 0.098% (IQR 0.026-0.758%). Over the course of echocardiographic follow-up, mean ∆GLS was -0.59% (±3.49%), mean ∆LVEF was -1.44% (±8.5%), and mean ∆E/e’ was -1.12(±3.23) in those with AF. Increasing AF burden was significantly associated with an accelerated decline in absolute global longitudinal strain in both univariable (ß= -0.12, p=0.002) and multivariable (ß= -0.11, p=0.003) models (Table 1/Figure 1). Conclusions In an older at-risk population, AF was frequent, and increasing AF burden was found to be independently associated with an accelerated decline in LV function. These findings support AF as an independent risk factor in the development of HF.

Understanding post-surgical decline in left ventricular function in primary mitral regurgitation using regression and machine learning models.

Class I echocardiographic guidelines in primary mitral regurgitation (PMR) risks left ventricular ejection fraction (LVEF) < 50% after mitral valve surgery even with pre-surgical LVEF > 60%. There are no models predicting LVEF < 50% after surgery in the complex interplay of increased preload and facilitated ejection in PMR using cardiac magnetic resonance (CMR). Use regression and machine learning models to identify a combination of CMR LV remodeling and function parameters that predict LVEF < 50% after mitral valve surgery. CMR with tissue tagging was performed in 51 pre-surgery PMR patients (median CMR LVEF 64%), 49 asymptomatic (median CMR LVEF 63%), and age-matched controls (median CMR LVEF 64%). To predict post-surgery LVEF < 50%, least absolute shrinkage and selection operator (LASSO), random forest (RF), extreme gradient boosting (XGBoost), and support vector machine (SVM) were developed and validated in pre-surgery PMR patients. Recursive feature elimination and LASSO reduced the number of features and model complexity. Data was split and tested 100 times and models were evaluated via stratified cross validation to avoid overfitting. The final RF model was tested in asymptomatic PMR patients to predict post-surgical LVEF < 50% if they had gone to mitral valve surgery. Thirteen pre-surgery PMR had LVEF < 50% after mitral valve surgery. In addition to LVEF (P = 0.005) and LVESD (P = 0.13), LV sphericity index (P = 0.047) and LV mid systolic circumferential strain rate (P = 0.024) were predictors of post-surgery LVEF < 50%. Using these four parameters, logistic regression achieved 77.92% classification accuracy while RF improved the accuracy to 86.17%. This final RF model was applied to asymptomatic PMR and predicted 14 (28.57%) out of 49 would have post-surgery LVEF < 50% if they had mitral valve surgery. These preliminary findings call for a longitudinal study to determine whether LV sphericity index and circumferential strain rate, or other combination of parameters, accurately predict post-surgical LVEF in PMR.

Correlation of Ductal size with Left Ventricular Systolic Function Changes by Echocardiography in Children after Transcatheter Closure of Patent Ductus Arteriosus in a Tertiary Care Hospital

Background: Transcatheter closure of Patent Ductus Arteriosus (PDA) is considered an excellent treatment option for children requiring PDA closure due to its low morbidity and mortality rates. Theoretically, after PDA closure, there should be a gradual improvement in left ventricular volume overload and remodeling. However, numerous studies have shown that there is a temporary decline in left ventricular function immediately following PDA closure. Objectives: To see the correlation of ductal size with changes in left ventricular systolic function by echocardiography in children undergoing transcatheter closure of PDA. Materials and methods: It was a cross sectional study. All pediatric inpatients ≥6 months of age, diagnosed as a case of PDA and planned for device closure were enrolled in the study. M-Mode, 2D, Color Doppler and 2D speckle tracking echocardiography was done by GE Echo machine Model VividS70N using probes 5MHz (5s) and 6MHz(6s). Electrocardiogram (ECG ) gated echo was done at base line (prior to closure of PDA), after 24 hour post closure and after 1 month post closure, in order to evaluate the immediate and short term changes in left ventricular systolic function from the baseline, using the following parameters: Left Ventricular Ejection Fraction (LVEF) and Left Ventricular Fractional Shortening (LVFS). The total sample size was 35. Data were collected on a pre-tested questionnaire. Data analysis was carried out by using the SPSS version 22.0 windows software. Continuous data were expressed as mean ±SD and analyzed by paired t-test. Categorical data were expressed as frequency and percentages. Correlation was seen using Pearson’s correlation. P-value &lt; 0.05 was considered statistically significant. Results: The mean age of the study subjects was 46.69 ± 41.8 months with mean body surface area of 0.56 ±0.25m² (0.32-1.3). Females were predominant with 74.3% and males were 25.7%. The mean PDA size was 3.35 ± 0.77mm and the LA: Aorta ratio was 1.45 ± 0.24. The LVEF, LVFS were reduced from 70.11±3.81 to 57.34±5.0, 39.28±3.14 to 32.0±4.54 respectively 24hours after device closure. This reduction of LVEF, LVFS were statistically significant (p&lt;0.01). At 1 month post device follow up all the parameters returned to near baseline level. PDA size was found to be negatively correlated with early changes in left ventricular functions i.e. larger the PDA size, greater is the reduction in LV function post PDA device. Conclusions: Transcatheter closure of PDA can lead to transient reduction in left ventricular systolic function which improves gradually after a month; however, close monitoring is required. Larger the PDA size, greater is the reduction in LV function. As such moderate to large PDAs should be followed up more cautiously and immediate timely intervention is needed, if severe deterioration is found.

Abstract 12295: Relation Between Withdrawal of Heart Failure Therapy and Left Ventricular Function After Improvement of Cancer Therapeutics Related Cardiac Dysfunction

Introduction: This study aimed to investigate withdrawal of guideline-directed medical therapy (GDMT) is associated with decline of left ventricular (LV) function after recovery from cancer therapeutics related cardiac dysfunction (CTRCD). Methods: From Mar 2015 to Dec 2021, 126 patients with improving CTRCD [defined as &gt;10% point improvement in LV ejection fraction (LVEF)] were identified. They were divided into 2 groups: patients who continued GDMT (GDMT+) and withdrew GDMT (GDMT-) after improvement of CTRCD. LV functional changes within 1 year and composite clinical outcome which was defined as hospitalization due to heart failure and all-cause death were compared between 2 groups. Results: The most frequent primary cancer was breast cancer [94 (74.6%)], followed by lymphoma [16 (12.7%)] and multiple myeloma [7 (5.6%)]. GDMT was withdrawn in 41 (32.5%) patients after improvement of CTRCD. Mean LVEF and LV global longitudinal strain (GLS) were comparable between 2 groups at the time of CTRCD diagnosis (LVEF: 44.6±8.5% in GDMT+ vs. 45.5±7.7% in GDMT-, p=0.592, LV GLS: 13.3±2.9% in GDMT+ vs. 13.6±2.7% in GDMT-, p=0.553), and when LVEF was improved (LVEF: 57.1±8.0% vs. 58.3±7.4%, p=0.457, LV GLS: 14.1±3.2% vs. 14.6±3.1%, p=0.398). Dividing into 4 groups according to LVEF at the time of CTRCD diagnosis, patients with LVEF 45-55% showed no significant difference of LV function after withdrawal of GDMT (LVEF: 65.4±3.9% vs. 63.5±4.1%, p=0.066, LV GLS: 16.9±2.2% vs. 16.2±1.8%, p=0.205), but patients with LVEF &lt;45% experienced significant decline of LVEF (LVEF: 52.7±6.4% vs. 48.7±7.2%, p=0.041, LV GLS: 11.8±2.7% vs. 11.2±2.4%, p=0.445). Withdrawal of GDMT was associated with poor composite clinical outcome in the multivariable-adjusted model [hazard ratio (95% CI) 1.38 (1.01 - 1.93), p=0.005]. Conclusions: Withdrawal of GDMT was associated with poor clinical outcome and decline of LV function in patients with improving CTRCD, particularly in patients with LVEF &lt;45%.

Myocarditis following COVID-19 vaccine: incidence, presentation, diagnosis, pathophysiology, therapy, and outcomes put into perspective. A clinical consensus document supported by the Heart Failure Association of the European Society of Cardiology (ESC) and the ESC Working Group on Myocardial and Pericardial Diseases.

Over 10 million doses of COVID‐19 vaccines based on RNA technology, viral vectors, recombinant protein, and inactivated virus have been administered worldwide. Although generally very safe, post‐vaccine myocarditis can result from adaptive humoral and cellular, cardiac‐specific inflammation within days and weeks of vaccination. Rates of vaccine‐associated myocarditis vary by age and sex with the highest rates in males between 12 and 39 years. The clinical course is generally mild with rare cases of left ventricular dysfunction, heart failure and arrhythmias. Mild cases are likely underdiagnosed as cardiac magnetic resonance imaging (CMR) is not commonly performed even in suspected cases and not at all in asymptomatic and mildly symptomatic patients. Hospitalization of symptomatic patients with electrocardiographic changes and increased plasma troponin levels is considered necessary in the acute phase to monitor for arrhythmias and potential decline in left ventricular function. In addition to evaluation for symptoms, electrocardiographic changes and elevated troponin levels, CMR is the best non‐invasive diagnostic tool with endomyocardial biopsy being restricted to severe cases with heart failure and/or arrhythmias. The management beyondguideline‐directed treatment of heart failure and arrhythmias includes non‐specific measures to control pain. Anti‐inflammatory drugs such as non‐steroidal anti‐inflammatory drugs, and corticosteroids have been used in more severe cases, with only anecdotal evidence for their effectiveness. In all age groups studied, the overall risks of SARS‐CoV‐2 infection‐related hospitalization and death are hugely greater than the risks from post‐vaccine myocarditis. This consensus statement serves as a practical resource for physicians in their clinical practice, to understand, diagnose, and manage affected patients. Furthermore, it is intended to stimulate research in this area.

The value of T1 mapping in patients with chronic mitral regurgitation

Abstract Introduction The management of asymptomatic patients with severe mitral regurgitation (MR) and normal left ventricular (LV) ejection fraction (EF) remains controversial. Progressive fibrosis secondary to volume overload may explain irreversible LV dysfunction post mitral valve surgery, even in patients in which the current guidelines for intervention are applied. Considering the limitation of the LV EF as a measurement of systolic function, cardiac magnetic resonance emerges as a new technique that can detect and quantify left ventricular fibrosis before irreversible decline in LV function occurs. Late gadolinium enhancement (LGE) is a recognised method of assessing replacement fibrosis. Native T1 and post contrast administration T1 mapping provide a useful tool for measuring extracellular volume (ECV) – a marker of interstitial fibrosis. The purpose of this study was to assess the presence of myocardial fibrosis by LGE and T1 mapping in patients with moderate and severe mitral regurgitation and normal ejection fraction. Method The study group consisted of 128 consecutive patients with moderate and severe mitral regurgitation with no indication of surgery, compared with a control group of 120 patients with mild MR, studied between 2018 and 2021. Patients with contraindications to CMR were excluded. Electrocardiogram, transthoracic echocardiography and cardiac magnetic resonance, including LGE and T1 mapping were performed in all patients. Circle CVi 42 was used for image post processing and ECV calculation. Statistical analysis was performed with SPPSS 21.0. A p value &amp;lt;0.05 was considered statistically significant. Results 37 patients with MR presented with different nonischemic patterns of LGE versus 8 controls. Precontrast administration T1 mapping showed significantly higher global T1 time in patients with MR (1178±129 ms) versus controls (974±115). Mean ECV was significantly higher in patients with MR versus controls (36% vs 22%). A comparison between patients with moderate and severe MR revealed significantly higher T1 values and ECV in patients with severe MR despite normal LV EF. During the followup 15 patients required intervention. Conclusion Our study has shown that patients with moderate and severe MR that do not meet the current guidelines criteria for surgery have significantly higher T1 times and ECV compared with those with mild MR. The assessment of interstitial fibrosis using CMR T1 mapping techniques may provide an important tool in selecting patients who may benefit from early surgery before irreversible myocardial fibrotic changes occur, thus improving long term prognosis. Funding Acknowledgement Type of funding sources: None.

Recovery From Left Ventricular Dysfunction.

The treatment of heart failure is an evolving field of cardiology, with increasingly available therapeutics and significant disease burden. With the effective treatments available, we see a substantial patient population whose once reduced ejection fraction (EF) has normalized. Studies have assessed the natural history of these patients with improved EF and found improved mortality as compared with those patients with persistently reduced EF, with some evidence stating that each 5% increase in left ventricular EF correlates with a 4.9-fold decrease in the odds of mortality. This prognostic divergence has led to the recognition of this subset of patients as having a unique heart failure diagnosis, distinct from heart failure with reduced EF (HFrEF) or heart failure with preserved EF and to the adoption of the term heart failure with recovered EF. These patients, despite having improved mortality, do retain some of the molecular and histologic changes seen in HFrEF and are still at risk for decline in left ventricular function and adverse cardiac events, particularly when medical therapy is stopped. This distinction between recovery of EF and true myocardial recovery led to recent guidelines recommending continuation of guideline-directed medical therapy indefinitely, as well as surveillance echocardiography.

Cardiovascular magnetic resonance-derived left ventricular intraventricular pressure gradients among patients with precapillary pulmonary hypertension.

Precapillary pulmonary hypertension (pPH) affects left ventricular (LV) function by ventricular interdependence. Since LV ejection fraction (EF) is commonly preserved, LV dysfunction should be assessed with more sensitive techniques. Left atrial (LA) strain and estimation of LV intraventricular pressure gradients (IVPG) may be valuable in detecting subtle changes in LV mechanics; however, the value of these techniques in pPH is unknown. Therefore, the aim of our study is to evaluate LA strain and LV-IVPGs from cardiovascular magnetic resonance (CMR) cines in pPH patients. In this cross-sectional study, 31 pPH patients and 22 healthy volunteers underwent CMR imaging. Feature-tracking LA strain was measured on four- and two-chamber cines. LV-IVPGs (from apex-base) are computed from a formulation using the myocardial movement and velocity of the reconstructed 3D-LV (derived from long-axis cines using feature-tracking). Systolic function, both LV EF and systolic ejection IVPG, was preserved in pPH patients. Compared to healthy volunteers, diastolic function was impaired in pPH patients, depicted by (i) lower LA reservoir (36 ± 7% vs. 26 ± 9%, P < 0.001) and conduit strain (26 ± 6% vs. 15 ± 8%, P < 0.001) and (ii) impaired diastolic suction (-9.1 ± 3.0 vs. ‒6.4 ± 4.4, P = 0.02) and E-wave decelerative IVPG (8.9 ± 2.6 vs. 5.7 ± 3.1, P < 0.001). Additionally, 11 pPH patients (35%) showed reversal of IVPG at systolic-diastolic transition compared to none of the healthy volunteers (P = 0.002). pPH impacts LV function by altering diastolic function, demonstrated by an impairment of LA phasic function and LV-IVPG analysis. These parameters could therefore potentially be used as early markers for LV functional decline in pPH patients.

Abstract 12899: CMR Derived Intraventricular Pressure Gradients Analysis Shows Impaired Left Ventricular Function in Precapillary Pulmonary Hypertension

Introduction: Precapillary pulmonary hypertension (pPH) predominantly harms the right ventricle. Still, due to ventricular interdependence, it also affects left ventricular (LV) function. Since LV ejection fraction (EF) is often preserved, more sensitive techniques may be better suited to detect LV dysfunction, such as LA strain or estimation of LV intraventricular pressure gradients (IVPG). However, the value of these techniques in pPH is still unknown. Hypothesis: Cardiovascular magnetic resonance (CMR) derived LA phasic function and LV-IVPG can detect LV dysfunction in pPH patients. Methods: pPH patients (n=31) and healthy controls (n=10), age- and sex-matched, underwent CMR imaging. LA phasic function and the LV-IVPG, calculating the pressure gradient between apex and base throughout the cardiac cycle, were analyzed using standard long-axis cines. Results: LV systolic function, both LVEF as well as the IVPG positive systolic ejection force, was preserved in pPH patients compared to healthy controls (p=0.90, p=0.08 resp.). However, diastolic function in pPH patients was impaired, depicted by 1. lower LA reservoir (patients vs. controls 26% ±9 vs. 37% ±7, p=0.001) and conduit strain (15% ±8 vs. 26% ±7, p=0.001), and 2. an impaired diastolic suction force, and decreased E-wave decelerative force, indicating a weaker passive filling in early to mid-diastole ( see Table ). Also, 11 pPH patients (35%) showed reversal of IVPG at systolic-diastolic transition, meaning that LV pressure temporarily exceeds LA pressure, whereas none of the healthy controls showed this pattern (p=0.04). Conclusions: pPH impacts LV function by altering diastolic function, demonstrated by an impairment of LA phasic function and LV-IVPG analysis. These parameters could therefore potentially be used as early markers for LV functional decline in pPH patients.

Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs.

Simple SummaryImmunotherapy is increasingly being used to treat solid tumors and lymphoproliferative diseases. The main classes of drugs are: HER-2-targeted therapies, CTLA-blockers, PD/PDL-1 inhibitors, CAR-T therapy. All these drugs are associated with meaningful cardiac toxicity, ranging from a transient decline of left ventricular function with complete reversibility to myocarditis with a high fatality rate.Cancer immunotherapy significantly contributed to an improvement in the prognosis of cancer patients. Immunotherapy, including human epidermal growth factor receptor 2 (HER2)-targeted therapies, immune checkpoint inhibitors (ICI), and chimeric antigen receptor-modified T (CAR-T), share the characteristic to exploit the capabilities of the immune system to kill cancerous cells. Trastuzumab is a monoclonal antibody against HER2 that prevents HER2-mediated signaling; it is administered mainly in HER2-positive cancers, such as breast, colorectal, biliary tract, and non-small-cell lung cancers. Immune checkpoint inhibitors (ICI) inhibit the binding of CTLA-4 or PD-1 to PDL-1, allowing T cells to kill cancerous cells. ICI can be used in melanomas, non-small-cell lung cancer, urothelial, and head and neck cancer. There are two main types of T-cell transfer therapy: tumor-infiltrating lymphocytes (or TIL) therapy and chimeric antigen receptor-modified T (CAR-T) cell therapy, mainly applied for B-cell lymphoma and leukemia and mantle-cell lymphoma. HER2-targeted therapies, mainly trastuzumab, are associated with left ventricular dysfunction, usually reversible and rarely life-threatening. PD/PDL-1 inhibitors can cause myocarditis, rare but potentially fulminant and associated with a high fatality rate. CAR-T therapy is associated with several cardiac toxic effects, mainly in the context of a systemic adverse effect, the cytokines release syndrome.

Descending thoracic aorta\u2013abdominal aortic bypass and bilateral renal arterial blood circulation reconstruction are effective in atypical coarctation of the aorta with heart failure: a case report

BackgroundThere are a lot of reports of the renal failure and heart failure due to coarctation of the aorta. However, there are no case reports in which revascularization dramatically improved left ventricular function in patients with progressive decline in left ventricular function. Herein, we present a rare case in which the left ventricular function was dramatically improved by surgical treatment for progressive left ventricular dysfunction due to atypical coarctation of the aorta.Case presentationA 58-year-old man underwent left axillary artery-bilateral femoral artery bypass at another hospital for atypical coarctation of the aorta due to Takayasu’s arteritis. Approximately 10 years later, he was re-hospitalized for heart failure, and the left ventricular ejection fraction gradually decreased to 28%. Computed tomography showed severe calcification and stenosis at the same site from the peripheral thoracic descending aorta to the lower abdominal aorta of the renal artery, and aortography showed delayed bilateral renal artery blood flow. An increase in plasma renin activity was also observed. Despite the administration of multiple antihypertensive drugs, blood pressure control was insufficient. We decided to perform surgical treatment to improve progressive cardiac dysfunction due to increased afterload and activated plasma renin activity. Descending thoracic aorta-abdominal aorta bypass and revascularization of the bilateral renal arteries via the great saphenous vein grafts were performed. Postoperative blood pressure control was improved, and the dose of antihypertensive drugs could be reduced. Plasma renin activity decreased, and transthoracic echocardiography 1.5 years later showed an improvement in contractility with a left ventricular ejection fraction of 58%.ConclusionIn atypical coarctation of the aorta in patients with decreased bilateral renal blood flow, heart failure due to renal hypertension, and progressive decrease in left ventricular contractility, descending thoracic aorta-abdominal aortic bypass and bilateral renal artery recirculation can be extremely effective.

Effects of cardiac medications on ventricular function in patients with Duchenne muscular dystrophy–related cardiomyopathy

The DMD Care Considerations Working Group Guidelines 2010 recommended treating cardiac dystrophinopathy with angiotensin-converting enzyme-inhibitor (ACEi) and beta-blocker (BB) therapy to prevent the progressive decline in left ventricular function expected from earlier, natural history studies. The aim of this research was to audit change in measures of left ventricular function over 8 years to 4 years before and 4 years after deploying an ACEi/BB combination systematically at a dedicated "cardiology-muscle" clinic. This is an institutionally registered, retrospective, case-file-based audit of serial echocardiographic measures of left ventricular fractional shortening accumulated over the period 1995 to 2015. Data from 104 genetically confirmed Duchenne muscular dystrophy (DMD) patients, aged 22.2 ± 5.3 years at data censure, were included. Mean age at first detection of left ventricular dysfunction was 15.1± 4.2 years, but older in those on maintenance steroid therapy (16.8± 4.2 vs 14.5± 4.1 years; P= .04). Group mean fractional shortening fell by 1.5%/year over the 4 years before therapy, but this decreased to 0.9%/year over the first 4 years after starting therapy. Analysis of limited left ventricular ejection fraction measures showed similar but nonsignificant changes. Neither age at detection of left ventricular dysfunction nor fractional shortening percent at time of therapy initiation affected the beneficial response. The results support the international DMD recommendations of the time. This combination of cardiac medications helps stabilize heart function. For the best long-term effects, therapy needs to be initiated no later than on first detection left ventricular impairment.

Left Atrial Remodeling Mechanisms Associated with Atrial Fibrillation.

Heart disease has always been one of the important diseases that endanger health and cause death. Therefore, it is particularly important to understand left atrium reconstruction and atrial fibrillation before heart image processing. The purpose of this paper is to provide an important review of the mechanisms of left atrial remodeling (LAR) associated with atrial fibrillation (AF). LAR refers to the spectrum of pathophysiological changes in (i) atrial structure and physiological function, and (ii) electric, ionic, and molecular milieu of the LA, in response to stresses imposed by conditions such as hypertension, myocardial ischemia, autonomic denervation and congestive heart failure. The main mechanisms of LAR include electrical remodeling, structural remodeling, metabolic remodeling, autonomic remodeling, neurohormones and inflammation, and other influencing factors. LAR is not only the basic mechanism of AF and heart failure, but also the pathophysiological basis of its progression. In clinical practice, AF is the most common persistent arrhythmia, and is believed to be the result of a combination of mechanisms that have triggers and maintenance mechanisms, including spontaneous ectopic pacing and multiple wavelet reentry. While LA electrophysiological, structural, and ultra-structural changes trigger AF, in turn, AF alters the LA electrical and structural properties that promote its maintenance and recurrence. Chronic AF leads to extensive changes in atrial cellular substructures, including loss of myofibrils, accumulation of glycogen, changes in mitochondrial shape and size, fragmentation of sarcoplasmic reticulum, and dispersion of nuclear chromatin. Electrical remodeling and structural remodeling of the atria during AF, involving structural changes and functional impairment of the left atrium, can lead to serious decline in left ventricular function and severe heart failure. Therefore, LAR and AF are inter-activating phenomena, and the resulting complications can cause serious disabling and fatal events. In this paper, we present (i) the mechanisms of LAR, in the form of structural, electrical, metabolic, and neurohormonal changes, and (ii) their interactive roles in initiating and maintaining AF. These in-depth understanding of the atrial remodeling mechanisms can in turn provide useful insights into the treatment of AF and heart failure.

Pharmacological targeting of mitochondrial function and reactive oxygen species production prevents colon 26 cancer-induced cardiorespiratory muscle weakness.

Cancer cachexia is a syndrome characterized by profound cardiac and diaphragm muscle wasting, which increase the risk of morbidity in cancer patients due to failure of the cardiorespiratory system. In this regard, muscle relies greatly on mitochondria to meet energy requirements for contraction and mitochondrial dysfunction can result in muscle weakness and fatigue. In addition, mitochondria are a major source of reactive oxygen species (ROS) production, which can stimulate increased rates of muscle protein degradation. Therefore, it has been suggested that mitochondrial dysfunction may be an underlying factor that contributes to the pathology of cancer cachexia. To determine if pharmacologically targeting mitochondrial dysfunction via treatment with the mitochondria-targeting peptide SS-31 would prevent cardiorespiratory muscle dysfunction, colon 26 (C26) adenocarcinoma tumor-bearing mice were administered either saline or SS-31 daily (3 mg/kg/day) following inoculation. C26 mice treated with saline demonstrated greater ROS production and mitochondrial uncoupling compared to C26 mice receiving SS-31 in both the heart and diaphragm muscle. In addition, saline-treated C26 mice exhibited a decline in left ventricular function which was significantly rescued in C26 mice treated with SS-31. In the diaphragm, muscle fiber cross-sectional area of C26 mice treated with saline was significantly reduced and force production was impaired compared to C26, SS-31-treated animals. Finally, ventilatory deficits were also attenuated in C26 mice treated with SS-31, compared to saline treatment. These data demonstrate that C26 tumors promote severe cardiac and respiratory myopathy, and that prevention of mitochondrial dysfunction is sufficient to preclude cancer cachexia-induced cardiorespiratory dysfunction.

The effect of prophylactic carvedilol on subclinical left ventricular dysfunction after 1 cycle FAC chemotherapy in breast cancer patients.

BackgroundDespite its efficacy, FAC regimen may cause fatal cardiotoxicity. Carvedilol may also exert additional antioxidant effects. This study aimed to assess the effect of carvedilol in preventing decline of left ventricular function in breast cancer patients receiving FAC regimen chemotherapy.MethodsThe study was a quasi-experimental study. The study subjects were consisted of breast cancer patients currently receiving post-first cycle FAC chemotherapy regimen in period of March – May 2019. The study subjects were divided into 2 groups: control and intervention group. In intervention groups, the patients consumed up titrated carvedilol with initial dose of 2 × 6.25 mg daily, follow-up echocardiography was performed for the patients in order to assess GLS score of left ventricle.ResultEighty patients were enrolled to the study, with each group consisted of 40 patients. Patient baseline characteristics were not significantly different between both groups. Left ventricular function was assessed using speckle tracking echocardiography and assessing the change of GLS score. Decrease of GLS score was higher in the intervention group compared to the control group, although the decrease was not statistically significant (0.767 ± 0.355 vs. 0.897 ± 0.526; p = 0.838). Percentage wise, similar findings were reported, albeit no significant (3.34 ± 1.65 vs. 3.46 vs. 2.58; p = 0.968).ConclusionsCarvedilol was not able to prevent the decline of subclinical left ventricular function after such chemotherapy cycle. However, it maybe more likely that the benefits appear in patients whose given larger cumulative dose of anthracycline and have multiple risk factors.