Changes In Left Ventricular Volume Research Articles

Leadless ultrasound-based cardiac resynchronization system in heart failure results from the SOLVE-CRT randomised sub-study and the primary population patient cohort

Abstract Background Despite the well-established role of CRT in heart failure, major limitations of CRT include an occasional incidence of unsuccessful coronary sinus (CS) lead placement, one third non-responders in conventional CRT patients and higher complications risk in CRT upgrade procedures. The WiSE® CRT System (EBR Systems, Inc) is designed to overcome these limitations. Prior non-randomized studies with the WiSE System have shown high implant success rates and improvement in LV remodeling and heart failure symptoms. Objectives The pivotal SOLVE-CRT study is comprised of two parts: a randomized part and the subsequent single-arm part enrolled during the pandemic. The primary safety endpoint is freedom from Type I (device & procedure-related) complications through 6 months and primary efficacy endpoint is the mean relative (%) change in left ventricular end systolic volume (LVESV) from baseline to 6 months. Method Between Jan. 2018 and Mar. 2020 the randomized part enrolled 108 participants for three indications: non-responders (NR), previously untreated, including acute and chronic lead failures (PU), and high-risk upgrades (HRU). All underwent device implantation and were then randomized in 1:1 ratio to Treatment (system turned ON) or Control (system turned OFF) groups. In the single arm, 75 participants had been enrolled within two indications: PU and HRU. The efficacy analysis of the entire randomised cohort included 99 participants (PU, HRU, NR). For the primary indication sub-population, 57 participants (PU, HRU) were analysed. Results Randomized Group: Results were available for 91 of the 99 patients. Significant improvements were seen between the Treatment and Control groups with a mean reduction in LVESV (-14.6% vs -5.2%, p=0.005), mean reduction in LVEDV (-8.1% vs -3.0%, p=0.027), mean increase in LVEF (5.4% vs 2.4%, p=0.048) and mean reduction in QRS (-41.9ms vs -1.7ms, p=0.001). Primary Indication Sub-Population Group: The primary indication sub-population also saw significant improvements between Treatment and Control group with a mean reduction in LVESV (-18.2% vs -3.1%, p=0.002), mean reduction in LVEDV (-11.6% vs -2.1%, p=0.004), mean increase in LVEF (5.7% vs 1.1%, p=0.025) and mean reduction in QRS (-38.0ms vs -3.1ms, p<0.001). Conclusion This pivotal SOLVE-CRT trial demonstrates that leadless, ultrasound-based endocardial pacing for heart failure is feasible and efficacious showing evidence of left ventricular remodelling and electrical response after 6 month in the primary population as well as in the sub-study group. Picture 1: Efficacy entire randomised population Picture 2: Efficacy primary indications population

The effect of cardiac resynchronisation therapy upgrade from right ventricular pacing on symptoms and functional clinical outcomes, results from the BUDAPEST-CRT Upgrade trial

Abstract Background Based on the results of the BUDAPEST-CRT Upgrade trial, in patients with intermittent or permanent right ventricular (RV) pacing and reduced left ventricular ejection fraction (HFrEF) upgrade to cardiac resynchronization therapy (CRT) reduces morbidity and mortality. Purpose Whether the substantial treatment effect of the CRT upgrade could also be detected in a better functional and exercise capacity is scarcely investigated. We examined the changes of the prespecified tertiary endpoints such as symptoms, quality of life (QoL), exercise capacity and natriuretic peptide measurement from baseline to 12 months. Methods In the BUDAPEST CRT Upgrade trial 360 HFrEF patients with a priorly implanted PM or ICD and >20% of RV pacing burden were randomly assigned to CRT-D upgrade (n=215) or ICD (n=145) in a 3:2 ratio. The prespecified tertiary endpoints were changes in quality of life measured by EQ-5D-3L, New York Heart Association (NYHA) functional class, 6-minute walk test (6-MWT), and NT-proBNP. When data of trial patients were unavailable due to death at 12 months, imputed values were used as 0 (6MWT) and 0 score (EQ-5D-3L) or a 5th grade (NYHA class). Responders were defined as >15% change of left ventricular end-systolic volume at 12 months. Results From baseline to 12 months, NYHA functional class improved in the CRT-D upgrade arm compared with the ICD only group [adjusted odds ratio (OR) 0.50; 95% CI 0.32-0.80; P=0.003]. According to the adjusted model there was a statistically significant decrease in the NT-proBNP [adjusted difference -1257 pg/mL; 95% CI -2287 – (-228); P=0.017]. In responders, the changes in NT-proBNP levels were significantly greater than in non-responders [adjusted difference -1635 pg/mL; 95% CI -2811 - (-459); P=0.007]. The progression of worsening of QoL attributed to ageing was moderated only by CRT-D upgrade [EQ-5D-3L difference by age -0.01; 95% CI -0.02 - (-0.003); P=0.004; interaction P=0.003]. 6MWT did not improve significantly in either group. Conclusions Patients receiving CRT upgrade showed a substantial improvement in symptoms and a significant decrease in natriuretic peptide levels, as compared to ICD alone, which was more pronounced in responders. Moreover, CRT-D upgrade could moderate the progression of worsening of quality of life attributed to ageing in this vulnerable, older patient population.

Empagliflozin to prevent progressive adverse remodelling after myocardial infarction (EMPRESS-MI): rationale and design.

Patients with a reduced left ventricular ejection fraction (LVEF) following an acute myocardial infarction (MI) are at risk of progressive adverse cardiac remodelling that can lead to the development of heart failure and death. The early addition of a sodium-glucose cotransporter 2 (SGLT2) inhibitor to standard treatment may delay or prevent progressive adverse remodelling in these patients. EMpagliflozin to PREvent worSening of left ventricular volumes and Systolic function after Myocardial Infarction (EMPRESS-MI) is a randomized, double-blind, placebo-controlled, multi-centre trial designed to assess the effect of empagliflozin on cardiac remodelling evaluated using cardiovascular magnetic resonance (CMR) in 100 patients with left ventricular systolic dysfunction following MI. Eligible patients were those ≥12h and ≤14days following acute MI, with an LVEF <45% by CMR. Patients were randomized to empagliflozin 10mg once a day or matching placebo. The primary outcome will be change in left ventricular end-systolic volume indexed to body surface area over 24weeks from randomization. Secondary endpoints include measures of left ventricular and atrial volumes, left ventricular mass, LVEF, and circulating cardiac biomarkers. EMPRESS-MI will assess the effect of the SGLT2 inhibitor empagliflozin on cardiac remodelling in patients with left ventricular systolic dysfunction after an acute MI.

Rate of Change in Cardiac Magnetic Resonance Imaging Measures Is Associated With Death in Duchenne Muscular Dystrophy.

Cardiovascular disease is the leading cause of death among patients with Duchenne muscular dystrophy (DMD). Identifying patients at risk of early death could allow for increased monitoring and more intensive therapy. Measures that associate with death could serve as surrogate outcomes in clinical trials. Duchenne muscular dystrophy subjects prospectively enrolled in observational studies were included. Models using generalized least squares were used to assess the difference of cardiac magnetic resonance measurements between deceased and alive subjects. A total of 63 participants underwent multiple cardiac magnetic resonance imaging and were included in the analyses. Twelve subjects (19.1%) died over a median follow-up of 5 years (interquartile range, 3.1-7.0). Rate of decline in left ventricular ejection fraction was faster in deceased than alive subjects (P<0.0001). Rate of increase in indexed left ventricular end-diastolic (P=0.0132) and systolic (P<0.0001) volumes were higher in deceased subjects. Faster worsening in midcircumferential strain was seen in deceased subjects (P=0.049) while no difference in global circumferential strain was seen. The rate of increase in late gadolinium enhancement, base T1, and mid T1 did not differ between groups. Duchenne muscular dystrophy death is associated with the rate of change in left ventricular ejection fraction, midcircumferential strain, and ventricular volumes. Aggressive medical therapy to decrease the rate of progression may improve the mortality rate in this population. A decrease in the rate of progression may serve as a valid surrogate outcome for therapeutic trials.

Effect of empagliflozin on left ventricular volumes in type 2 diabetes or prediabetes heart failure patients with reduced ejection fraction

Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin are antidiabetic drugs that have recently been reported to have cardio-protective action; however, their effect on cardiac structure and function in heart failure with reduced ejection fraction (HFrEF) has not yet been determined. This study evaluates the efficacy of empagliflozin on left ventricular (LV) volumes in type 2 diabetes or prediabetes patients with HFrEF. Methods: This randomised, double-blind, trial study was conducted on 104 patients with type 2 diabetes or prediabetes with HFrEF referred to Imam Khomeini and Golestan hospitals in Ahvaz, Iran. The patients were randomised to receive empagliflozin (10 mg once daily) in addition to standard treatments of HFrEF or receive only standard treatments (control group) for six months. During the six months of follow-up, changes in LV volumes, LVEF, hospitalisation for heart failure (HF) were evaluated. Results: Empagliflozin reduced LVEDVI and LVESVI by 10.0 and 8.0 mL/m2 (p < 0.0001). Furthermore, a significant increase in LVEF was observed in the empagliflozin group (p < 0.0001) without any significant change in the control group (p = 0.389). The hospitalisation rate was lower in the empagliflozin group than the control group (3.8% vs. 23.1%; p = 0.008). Conclusions: Empagliflozin is effective in reducing LV volumes and hospitalisation rate in patients with type 2 diabetes and prediabetes and HFrEF. Therefore, treatment with empagliflozin for six months was associated with a significant reduction in adverse cardiovascular outcomes in these patients.

Assessing fluid responsiveness with ultrasound in the neonatal intensive care setting: the mini-fluid challenge.

The mini-fluid challenge (MFC) can guide individualised fluid therapy and prevent fluid overload and associated morbidity in adult intensive care patients. This ultrasound test is based on the Frank-Starling principles to assess dynamic fluid responsiveness, but limited MFC data exists for newborns.This brief report describes the feasibility of the MFC in 12 preterm infants with late onset sepsis and 5 newborns with other pathophysiology. Apical views were used to determine the changes in left ventricular stroke volume before and after a 3ml/kg fluid bolus was given over 5min. Four out of the 17 infants were fluid responsive, defined as a post-bolus increase in stroke volume of 15% or more. Conclusion: The MFC was feasible and followed the physiological principles of stroke volume and extravascular lung water changes and 24% were fluid responsive. The MFC could enable future studies to examine whether adding fluid responsiveness to guide fluid therapy in newborns can reduce the risk of fluid overload. What is Known: • Fluid overload is associated with morbidity and mortality. • The mini-fluid challenge (MFC) provides a personalised approach to fluid therapy. What is New: • The MFC is feasible in newborns. • The MFC followed the physiological principles of stroke volume and extravascular lung water changes.

Discovering the Clinical Relevance of Heart-Lung Interactions.

In 1978, Dr. Pinsky's scientific career became firmly directed toward understanding the deeper meaning of heart-lung interactions. This would define his focus for the next 45 yr. At the time, he and colleagues studied the effects of changes in intrathoracic pressure on left ventricular performance in humans, documenting that the primary effect of large negative swings in intrathoracic pressure was to increase left ventricular transmural ejection pressure, and thus left ventricular afterload, selectively. They concluded that large intrathoracic pressure changes directly influence cardiac performance. This fundamental observation was followed by many additional observations in both highly invasive animal studies supported by less invasive clinical studies, which showed that intrathoracic pressure-induced changes in the gradients for venous return to the heart and left ventricular ejection from the heart disproportionately affected both right ventricular and left ventricular function. The direct clinical implications of these results form the rationale for use of continuous positive airway pressure as a primary treatment of acute cardiogenic pulmonary edema and immediate endotracheal intubation for acute upper airway obstruction. These findings subsequently led to the practical use of dynamic changes in left ventricular stroke volume and the associated arterial pulse pressure during positive-pressure ventilation to identify volume responsiveness and, thus, to personalize resuscitation efforts in the treatment of acute cardiovascular insufficiency.

Effects of Mitral Valve Surgery on Ventricular Arrhythmia in Mitral Valve Prolapse Patients: Five-Year Eollow-up.

Aim To evaluate the effect of mitral valve (MV) repair and replacement on the incidence of ventricular arrhythmias (VA) and to identify risk factors for the persistence of VA in patients with MV prolapse and severe mitral regurgitation (MR) during a mid-term follow-up.Material and methods A single-site observational, prospective study successively enrolled 30 patients (mean age, 55.2±9.9 years, 60% men) who underwent MV repair or replacement for severe MR due to MV prolapse or chordal avulsion. Transthoracic echocardiography and Holter monitoring were performed in all patients before and annually after surgery. A pathomorphological study of MV fragments excised during surgery was performed.Results During the five-year follow-up period (144 person-years), one case of sudden cardiac death outside a health care facility was recorded. MR severity progressed in three patients after MV repair. The total number of all VAs decreased during the follow-up period, with a significant decrease in the number of paroxysms of unstable ventricular tachycardia during the first two years after surgery. The presence of VA in the postoperative period was correlated with the severity of postoperative left ventricular (LV) remodeling: end-diastolic volume (EDV) (rs=0.69; p=0.005), LV ejection fraction (EF) (rs = -0.55; p=0.004) and severity of MV myxomatous alterations according to histological study data (rτ=0.58; p=0.045). The beta-blocker treatment did not influence the VA frequency and severity (rs= -0.18; p=0.69). According to a univariate regression analysis only EDV (p = 0.001), LVEF &lt;50% (p = 0.003), and myxomatous MV degeneration (p = 0.02) were risk factors for persistent ventricular tachycardia in the postoperative period.Conclusion Surgical intervention on MV in patients with MV prolapse and severe MR decreased the number of cases of malignant VAs and was correlated with the postoperative changes in LV volume and function, as well as the severity of MV myxomatous alterations.

Effect of balloon pulmonary angioplasty on cardio-ankle vascular index and biventricular remodeling in patients with chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by organized pulmonary thrombi, and pulmonary endarterectomy is the only curative treatment. Since balloon pulmonary angioplasty (BPA) has become an established therapeutic option for inoperable CTEPH, prognosis has improved. Recent reports suggest that arterial stiffness evaluated using the cardio-ankle vascular index (CAVI) may play an important role in the cardio-vascular interaction in CTEPH; however, the details remain unclear. This study aimed to clarify the role of CAVI in CTEPH through hemodynamic changes and ventricular remodeling after BPA. A total of 23 patients with CTEPH who had undergone BPA were enrolled in this study. The mean pulmonary artery pressure (mPAP) and CAVI significantly decreased after BPA [mPAP, 34 (26-45) mmHg to 20 (19-24) mmHg, p < 0.0001; CAVI, 9.4 (8.0-10.3) to 8.3 (7.5-9.6), p = 0.004]. The echocardiographic right ventricle was significantly decreased, and the left ventricular volume was significantly increased after BPA, indicating significant biventricular remodeling after BPA. Changes in CAVI (ΔCAVI) significantly correlated with changes in mPAP (r = 0.45, p = 0.03). Additionally, ΔCAVI was significantly correlated with changes in both right ventricular area and left ventricular volume. Arterial stiffness, evaluated using the CAVI, improved after BPA. Changes in CAVI were significantly correlated with changes in pulmonary arterial pressure and biventricular remodeling. CAVI may play an important role in cardiovascular interactions in patients with CTEPH.

Effect of empagliflozin on cardiac remodelling in South Asian and non-South Asian individuals: insights from the EMPA-HEART CardioLink-6 randomised clinical trial

BackgroundThis exploratory sub-analysis of the EMPA-HEART CardioLink-6 trial examined whether the previously reported benefit of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on left ventricular (LV) mass (LVM) regression differs between individuals of South Asian and non-South Asian ethnicity.MethodsEMPA-HEART CardioLink-6 was a double-blind, placebo-controlled clinical trial that randomised 97 individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) to either empagliflozin 10 mg daily or placebo for 6 months. LV parameters and function were assessed using cardiac magnetic resonance imaging. The 6-month changes in LVM and LV volumes, all indexed to baseline body surface area, for South Asian participants were compared to those for non-South Asian individuals.ResultsCompared to the non-South Asian group, the South Asian sub-cohort comprised more males, was younger and had a lower median body mass index. The adjusted difference for LVMi change over 6 months was -4.3 g/m2 (95% confidence interval [CI], -7.5, -1.0; P = 0.042) for the South Asian group and -2.3 g/m2 (95% CI, -6.4, 1.9; P = 0.28) for the non-South Asian group (Pinteraction = 0.45). There was no between-group difference for the adjusted differences in baseline body surface area-indexed LV volumes and LV ejection fraction.ConclusionsThere was no meaningful difference in empagliflozin-associated LVM regression between South Asian and non-South Asian individuals living with T2DM and CAD in the EMPA-HEART CardioLink-6 trial.Trial registrationClinicalTrials.gov Identifier: NCT02998970 (First posted on 21/12/ 2016).

Left ventricular reverse remodeling following initiation of sacubitril/valsartan for heart failure with reduced ejection fraction and low blood pressure

Abstract Background Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) &amp;lt; 50%. Since sacubitril/valsartan was reported to be more potent than renin-angiotensin-aldosterone system inhibitors for lowering blood pressure, HF patients with low blood pressure were not included in most clinical studies as a result of sacubitril/valsartan administration, and average systolic blood pressure of most enrolled patients was around 120 mmHg. Thus, the effect of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for HF patients with LVEF &amp;lt; 50% and low blood pressure, remains uncertain. Purpose The aim of this study was to examine the effect of sacubitril/valsartan on LV reverse remodeling after initiation of the maximum tolerated dose of sacubitril/valsartan for HF patients with LVEF &amp;lt; 50% and systolic blood pressure ≤ 100 mmHg, and a comparison of its efficacy with that for patients with systolic blood pressure &amp;gt; 100 mmHg. Methods We retrospectively studied 164 HF patients with LVEF &amp;lt; 50% who were treated with sacubitril/valsartan from two institutions. Echocardiography was performed before and 9.5 ± 5.1 months after initiation of maximum tolerated dose of sacubitril/valsartan. Results sacubitril/valsartan was discontinued for 17 (10.4%) as decided by the attending physician mainly due to hypotension. The prevalence of discontinuation of sacubitril/valsartan for the low blood pressure group was higher than that for the non-low blood pressure group, but the difference was not statistically significant (16.0% vs. 9.4%, P = 0.32). No serious adverse events occurred during this study. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group than for the non-low blood pressure group (165 ± 106 mg vs. 238 ± 124 mg, P = 0.017). As expected, significant LV reverse remodeling was observed in the non-low blood pressure group after initiation of sacubitril/valsartan. It was noteworthy that significant LV reverse remodeling was also observed in the low blood pressure group after initiation of sacubitril/valsartan (LV end-diastolic volume: 177.3 ± 66.0 mL vs. 137.7 ± 56.1 mL, P&amp;lt;0.001, LV end-systolic volume: 131.6 ± 60.3 mL vs. 94.6 ± 55.7 mL, P&amp;lt;0.001, LVEF: 26.8 ± 10.3% vs. 33.8 ± 13.6%, P = 0.015). Relative changes in LV volumes and LVEF after initiation of sacubitril/valsartan were similar for the two groups (Figure). Conclusions Significant LV reverse remodeling can occur after initiation of sacubitril/valsartan even in HF patients with LVEF &amp;lt; 50% and systolic blood pressure ≤ 100 mmHg if tolerated. This finding is expected to offer new insights for better management of HF patients.Figure

Associations of 2013 and 2021 ESC definitions of left bundle-branch block with mechanical dyssynchrony and CRT-induced reverse remodeling

Abstract Background In 2021, a new and stricter ECG-based definition of LBBB was proposed and implemented in the European Society of Cardiology (ESC) guidelines on cardiac pacing and cardiac resynchronization therapy (CRT). Aim To investigate the association between the 2021 and the 2013 LBBB definitions with CRT-induced left ventricular (LV) reverse remodeling, as well as mechanical dyssynchrony. Methods CRT patients (n=191) were retrospectively investigated. Pre-CRT digitally stored ECGs were analyzed and categorized according to the LBBB definition of 2013 (LBBB-2013) and the 2021 (LBBB-2021). Mechanical dyssynchrony (Dyss) was assessed pre-CRT using 2D-echocardiography and was defined as the presence of apical rocking and/or septal flash. CRT-induced LV reverse remodeling was measured as the relative change of left ventricular end systolic volume (LVESV) at 12 ± 6 months after CRT compared to baseline. Results Patients’ characteristics were as follows; age 70 ± 10 years, 69% males and NYHA class 2.7 ± 0.5. QRS width was 156 ± 18 ms and LVEF 33 ± 11%, and 52% had ischemic etiology. Dyss was present in 59% of the population. The percentage of the cohort that was considered to have LBBB was considerably lower according to the LBBB-2021 than according to the LBBB-2013 (18 vs. 57% respectively). Similarly, percentages of patients with LBBB+Dyss were 16 and 46% according to LBBB-2021 and LBBB-2013 respectively, with a respective Kappa coefficient of 0.16 and 0.47 (Figure A). At CRT follow up, LBBB-2013 patients showed significantly more LV reverse remodeling compared to non-LBBB patients (P &amp;lt; 0.001), while there was no significant difference between patients with LBBB-2021 and non-LBBB (P = 0.09, Figure B). Conclusion The LBBB definition proposed in the 2021 ESC guidelines excludes many patients from a class I indication for CRT. It is less associated with mechanical dyssynchrony and with CRT-induced LV reverse remodeling than the 2013 LBBB definition. Therefore, the new LBBB definition appears to be counterproductive with regards to selection of CRT patients.

The effect of bariatric surgery type on cardiac reverse remodelling

Abstract Introduction Bariatric surgery has been shown to improve adverse cardiac remodelling associated with obesity. Three operations are commonly performed: Roux-en-Y Gastric Bypass (RYGB), Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Adjustable Gastric Band (LAGB). Whilst all three of these procedures result in weight loss, it is currently unclear as to which procedure is most effective at reversing cardiac remodelling. Purpose We assessed differences in cardiac remodelling following each type of surgery using cardiac magnetic resonance (CMR) imaging. Methods 58 patients underwent bariatric surgery (26 RYGB, 22 LSG and 10 LAGB) with CMR before and after surgery, including 46 with short-term (median 251, 219 and 273 days) and 43 with long-term (median 1026, 983 and 1027 days) follow-up. CMR was used to assess cardiac volumes, LV mass (LVM) and LV mass:volume ratio (LVMVR – a marker of concentric remodelling). Adipose tissue depots were also assessed during the scan, including visceral adipose tissue (VAT) at L5 level and epicardial adipose tissue (EAT) (manual contouring in end-ventricular systole on short axis slices from the mitral valve to the apex). Results Changes in percentage body weight were similar between surgery groups in the short term, but appeared to diverge in the longer term (LSG vs LAGB, p=0.039; RYGB vs LAGB, p=0.341) (Figure 1A). Percentage change in VAT and EAT however where significantly greater following RYGB and LSG compared to LAGB at both short- and long-term time points (Figure 1B). Changes in left ventricular end diastolic volume (LVEDV) were similar between groups in both the short term and long term (Figure 2A). We observed a significant difference in LVM change following RYGB or LSG versus LAGB (Figure 2B). This change in LVM at the long-term time point correlated with change in VAT normalised to body weight (r=0.3399, p=0.0368, Figure 2C). Finally, there was a significant decrease in LVMVR at the long-term time point following both RYGB (p=0.006) and LSG (p=0.021), whereas no such change was observed following LAGB (p=0.912). Conclusions Our results suggest that RYGB and LSG are significantly better at decreasing body adipose depots than LAGB. This greater reduction in visceral adipose tissue may account for the greater cardiac reverse remodelling seen with RYGB and LSG compared to LAGB.Figure 1Figure 2

Abstract 14700: Associations of Left Ventricular Structure With Cumulative Systolic Blood Pressure Load: A Report From Women’s Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study

Background: Recent studies have identified cumulative systolic blood pressure load to be associated with increased risk of adverse cardiovascular disease (CVD) outcomes. Similarly, associations between left ventricular (LV) structure and CVD events have long been recognized. Purpose: The purpose of this study was to assess the association between cumulative systolic blood pressure (CuSBP) load and LV structure in women with suspected ischemia with no obstructive coronary arteries (INOCA). Methods: Women enrolled in the Women’s Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction (WISE-CVD) study (NCT00832702) underwent cardiac magnetic resonance imaging (CMRI) for LV structure and those (n= 225) who had at least 2 blood pressure (BP) measures recorded at a single site before their baseline CMRI were included in this analysis. Cumulative systolic BP (CuSBP) was defined as systolic BP (SBP) ≥ 130 divided by all SBP readings and each mean value multiplied by the years. LV remodeling index was defined as the ratio between LV mass and LV end diastolic volume (LVEDV). Results: The mean age was 55±10 years, body mass index (BMI) 26.3 ± 5.5 kg/m 2 , 36% had a history of hypertension, number of BP medications was mean 2.7 ± 1.6 [median 2 (range 0, 8)], and SBP and DBP were 126 ± 15 and 66 ± 10 mmHg respectively. Age, BMI and history of hypertension were significantly associated with higher CuSBP load. In univariate analyses, LV end diastolic volume and LV end systolic volume decreased, and LV remodeling index increased across CuSBP quartiles while LV mass index did not significantly differ among the quartiles (Figure 1) . In multivariable regression analysis, the association between CuSBP and LV mass index and LV remodeling index remained significant. Conclusions: Among women with suspected INOCA, higher CuSBP load was associated with greater LV mass index and concentric LV remodeling independent of age. Changes in LV volumes may represent age-related changes in LV structure.

Abstract 16721: Concentrations of Troponin I but Not Cardiac Troponin T Are Associated With 7-year Changes in Left Ventricular Structure and Function in Older Adults: The Atherosclerosis Risk in Community (ARIC) Study

Introduction: High-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are strongly associated with incident heart failure (HF) and left ventricular (LV) remodeling. Their associations with longitudinal changes in cardiac structure and function are less clear. Methods: Among 1,908 participants in the Atherosclerosis Risk in Communities (ARIC) study who were free of coronary disease, HF, or atrial fibrillation and had echocardiography at study Visits 5 (2011-2013) and 7 (2017-2019), we assessed the associations of log-transformed hs-cTnT and hs-cTnI at Visit 5 with absolute changes in LV structure and function between Visit 5 and 7 (median of 6.6 [IQR 6.1-7.0] years) using multivariable linear regression with the exposures modeled as restricted cubic spline models. Models were adjusted for age, sex, race, BMI, diabetes, hypertension and eGFR at Visit 5, blood pressure and heart rate at both visits. Results: At Visit 5, the mean age (years) was 74 (SD 4), 60% were female, 24% reported Black race and the median (p25-p75) concentrations of hs-cTnT and hs-cTnI were 9 (6-13) ng/L and 2.7 (1.9-4.0) ng/L respectively. In adjusted models, higher hs-cTnI concentration was associated with 7-year decline in LV systolic function (ejection fraction, global longitudinal and circumferential strain; Figure ). In contrast, hs-cTnT was not consistently associated with changes in cardiac function. Changes in hs-cTnI, but not hs-cTnT, were also associated with greater increases in left atrial volume. Neither were associated with changes in LV mass or volume. Conclusions: Higher hs-cTnI, but not hs-cTnT, concentrations are associated with greater declines in LV function over ~7 years in late life independent of traditional cardiovascular risk factors. These findings support previous findings of cTnI to be more cardiac specific than cTnT.

Left ventricular strain-volume loops and myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy

BackgroundThe left ventricular strain–volume loop (SVL) combines changes in global longitudinal strain (GLS) and LV volume across a cardiac cycle, providing insight into cardiac dynamics. This study explored the association between left ventricular SVL and presence of fibrosis, assessed with late gadolinium enhancement, in patients with Duchenne muscular dystrophy (DMD). Methods and results34 pediatric patients with DMD were included. Feature tracking analysis was used to assess endocardial GLS and volumetric measurements to construct the SVL. Mean age at the time of assessment was 14 ± 3 and 11 ± 2 years old (p < 0.01) in the group with (n = 18) versus without fibrosis (n = 16), respectively. Left ventricular ejection fraction was not significantly different between groups (fibrosis: 56.4 ± 3.8% versus without fibrosis: 54.0 ± 6.3%, p = 0.18). After adjusting for age, the late diastolic slope of the SVL was significantly associated with presence of fibrosis (OR 0.39 [95% CI 0.18–0.85]; area under the receiver operating characteristic curve: 0.83 [95% CI 0.70–0.97]) No significant association was observed for peak strain and fibrosis (OR 1.15 [95% CI 0.86–1.546]). ConclusionA lower late diastolic slope of the left ventricular SVL, related to the interplay between longitudinal deformation and volume changes late in diastole, is associated with presence of myocardial fibrosis in pediatric patients with DMD.

Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure

Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve clinical outcomes in patients with heart failure (HF), but mechanisms of action are incompletely understood. In the EMPA-TROPISM trial, empagliflozin reversed cardiac remodeling and increased physical capacity in stable non-diabetic patients with systolic HF. Here we explore, post hoc, whether treatment effects in this cohort, comprising patients who had a high prevalence of iron deficiency, were related to iron metabolism. Myocardial iron content estimated by cardiac magnetic resonance T2* quantification increased after initiation of empagliflozin but not placebo (treatment effect: P = 0.01). T2* changes significantly correlated with changes in left ventricular volumes, mass and ejection fraction, peak oxygen consumption and 6-minute walking distance; concomitant changes in red blood cell indices were consistent with augmented hematopoiesis. Exploratory causal mediation analysis findings indicated that changes in myocardial iron content after treatment with empagliflozin may be an important mechanism to explain its beneficial clinical effects in patients with HF.ClinicalTrials.gov: NCT03485222.

Reverse Remodeling Effects of Sacubitril-Valsartan: Structural and Functional Optimization in Stage C Heart Failure

BackgroundSacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, reduces all-cause mortality as well as the rate of heart failure hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF). This study aimed to elucidate the benefits of initiating sacubitril-valsartan on ventricular remodeling in patients previously optimized on guideline directed medical therapy. MethodsIn this prospective, single-arm longitudinal study, 40 patients with HFrEF who were optimized on guideline-directed medical therapy were transitioned to sacubitril-valsartan. The primary end-point was the change in left ventricular (LV) volume at 1 year as assessed by three dimensional transthoracic echocardiography. Other echocardiographic endpoints included change in LV function and change in right ventricular (RV) size and function. ResultsThe mean age was 55 ± 12 years and 63% were male. At 1 year, LV end-diastolic volume decreased from 242 ± 71 to 157 ± 57 ml (p <0.001) with a corresponding increase in LV ejection fraction from 32 ± 7 to 44 ± 9 % (p <0.001). RV end-diastolic volume decreased from 151 ± 51 to 105 ± 45 ml (p <0.001). While RV ejection fraction did not change (51 ± 8 vs 51 ± 10; p = 0.35), RV GLS improved from -14.9 ± 3.4 % to -19.3 ± 4.3 % (p <0.001) ConclusionWhen added to standard medical therapy for heart failure, sacubitril-valsartan induces significant remodeling of both the right and left ventricles as assessed by 3D echocardiography.

Colchicine added to standard therapy further reduces fibrosis in pigs with myocardial infarction.

The anti-inflammatory drug colchicine improves the outcome of patients with myocardial infarction (MI). As an intense inflammatory and fibrotic response after MI may lead to scar expansion and left ventricular (LV) remodeling, the clinical benefit of colchicine could be related to a positive effect on the infarct scar and LV remodeling. Pigs underwent left anterior descending artery occlusion through an angioplasty balloon for 90 min and were then randomized into two groups: standard therapy [ACE inhibitor, beta blocker, mineralocorticoid receptor antagonist (MRA), aspirin] plus colchicine (n = 14) or standard therapy alone (n = 13). The pigs were treated for 30 days and underwent two cardiac magnetic resonance (CMR) scans at 72 h and 30 days. The pigs were then sacrificed the day after the second CMR. The primary efficacy end point was the extent of fibrosis in the infarct zone (calculated on eight samples from this zone and averaged). In the hearts explanted after 31 days, pigs in the colchicine group had less fibrosis in the infarct zone than the other animals [41.6% (20.4-51.0) vs. 57.4% (42.9-66.5); P = 0.022]. There was a trend toward a higher myocardial salvage index (MSI; an index of the efficacy of revascularization) in pigs on colchicine (P = 0.054). Conversely, changes in LV volumes, ejection fraction and mass did not differ between groups. Colchicine therapy for 1 month after reperfused MI further reduces myocardial fibrosis when added to standard therapy, while it does not have additional effects on LV remodeling.

Left ventricular reverse remodeling following initiation of sacubitril/valsartan for heart failure with reduced ejection fraction and low blood pressure.

Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) < 50%. However, the impact of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for such patients with low blood pressure, remains uncertain. We retrospectively studied 164 HF patients with LVEF < 50% who were treated with sacubitril/valsartan from two institutions. Echocardiography was performed before and 9.5 ± 5.1months after initiation of maximum tolerated dose of sacubitril/valsartan. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group (≤ 100mmHg in systole) than for the non-low blood pressure group (> 100mmHg in systole) (165 ± 106mg vs. 238 ± 124mg, P = 0.017). As expected, significant LV reverse remodeling was observed in the non-low blood pressure group after initiation of sacubitril/valsartan. It was noteworthy that significant LV reverse remodeling was also observed in the low blood pressure group after initiation of sacubitril/valsartan (LV end-diastolic volume: 177.3 ± 66.0mL vs. 137.7 ± 56.1mL, P < 0.001, LV end-systolic volume: 131.6 ± 60.3mL vs. 94.6 ± 55.7mL, P < 0.001, LVEF: 26.8 ± 10.3% vs. 33.8 ± 13.6%, P = 0.015). Relative changes in LV volumes and LVEF after initiation of sacubitril/valsartan were similar for the two groups. In conclusion, significant LV reverse remodeling occurred after initiation of sacubitril/valsartan, even in HF patients with LVEF < 50% and systolic blood pressure ≤ 100mmHg.