Improvement In Diastolic Function Research Articles

Fenofibrate modulates cardiac energy metabolism in moderate-severe aortic stenosis: a mechanistic double-blinded randomised controlled MR trial

Abstract Background Aortic stenosis (AS) is associated with impaired cardiac metabolism and high-energy phosphate production which can further exacerbate the progression to HF. Myocardial lipid accumulation and reduced production of high-energy phosphates have important implications for both systolic and diastolic heart function in AS. Peroxisome proliferator-activated receptor alpha (PPAR-alpha agonist, has the potential to optimise cardiac substrate metabolism, thereby, may be effective in improving cardiac dysfunction and functional capacity in AS. Methods In this prospective, randomized, double-blind, placebo-controlled study, patients with moderate-to-severe asymptomatic AS (n=72) were randomly assigned to Fenofibrate 200 mg daily or matching placebo for 6 months in 4:1 fashion. Of the total 72 participants, 59 received Fenofibrate and 13 received placebo. All subjects underwent cardiac magnetic resonance (CMR) and exercise testing at 0 and 6 months, with follow-up data available in 47 patients. The primary end point was change in myocardial triglyceride content (MTG) determined by proton magnetic resonance spectroscopy (1H-MRS). Secondary outcome measures included change in cardiac energetics (PCr/ATP) determined by phosphorus magnetic resonance spectroscopy (31P-MRS), left ventricular strain determined by myocardial tagging and exercise capacity i.e. peak VO2 assessment via cardiopulmonary exercise testing. Results Cardiac energetics (PCr/ATP) showed statistically significant improvement in the Fenofibrate group (0.14 ± 0.48; CI: - 0.03, 0.30; p=0.05) vs placebo group (0.11 ± 0.75; CI -0.42, 0.65; p=0.64). There was also significant reduction in MTG in the Fenofibrate group (mean change -0.40 ± 0.97; 95% CI -0.74, -0.06; p=0.02). MTG content also reduced in the placebo group (mean change -0.41 ± 0.26, 95% CI -1.10, 0.18, p 0.13), but the reduction was not statistically significant. Though no significant changes were seen in the systolic function parameters, there was a significant improvement in diastolic function in the fenofibrate group only (peak diastolic longitudinal strain rate 9.6, 95% CI: 1.13, 18.1; p = 0.02). Peak VO2 did not show any significant improvement in either group. Conclusions Fenofibrate works as a metabolic modulator upregulating fatty acid metabolism in pressure overload AS hearts. Such modulation is associated with an improvement in cardiac energetics and diastolic function in moderate-severe AS.Main results from baseline to 6 monthsBaseline demographic and CMR parameters

Early echocardiographic changes and reverse remodeling after transcatheter aortic valve implantation

Abstract Introduction Our hospital is a tertiary centre performing more than 500 transcatheter aortic valve implantation (TAVI) procedures annually. In this study we present early echocardiographic changes post-TAVI. Methods Clinical data collection and comprehensive echocardiography was performed the day before and 3.5±1.6 months after TAVI. Data analysis compared pre- and post-TAVI evaluations. Results A total of 101 patients were analyzed. Mean age was 80.1±6.8 years and 40% were female. TAVI was performed transfemorally in all patients, with 83% receiving a balloon expandable valve. NYHA class improved from 2.5±0.6 to 1.4±0.5 after TAVI (p<0.001) Echocardiographic parameters are summarized in Table. Global longitudinal strain (GLS) improved from -17±4% pre-TAVI to -18±4% post-TAVI (p<0.001), with no notable change in LVEF. A significant reverse remodeling with ≥10% reduction in left ventricular mass index (LVMi) was observed in 52% of patients following TAVI (from 124±32 to 110±29 g/m2, p<0.001) (Figure). Predictors of LVMi reduction were pre-TAVI LVMi and absence of comorbid hypertension (OR=1.02, 95% CI=1-1.03, p=0.03 and OR=0.31, 95% CI=0.11-0.84, p=0.02 respectively). There was no significant improvement in diastolic function, including left atrial strain. Conclusions Early post-TAVI assessments showed significant reverse remodelling with improvements in GLS and LVMi after TAVI. Predictors of LVMi reduction post-TAVI were absence of comorbid hypertension and higher baseline LVMi. There was no notable changes in diastolic function.

Relationship between changes in renal function after acute phase of tafamidis administration and left ventricular diastolic function at mid-term follow-up in transthyretin cardiac amyloidosis

Abstract Background A large number of heart failure (HF) patients present with various degrees of renal dysfunction, known as cardio-renal syndrome. Renal impairment in HF patients is also associated with an independent risk factor for morbidity and mortality. Transthyretin (TTR) amyloidosis (ATTR) is characterized by disintegrated liver-derived TTR that accumulates as amyloid fibrils in the myocardium, leading to initially presenting as left ventricular (LV) hypertrophy and LV diastolic dysfunction. Although there is no proven therapy for patients with ATTR cardiomyopathy (ATTR-CM), tafamidis meglumine, a TTR stabilizer, has been associated with favorable outcomes. Although the kidneys are also an important organ where amyloid deposition occurs, the effect of tafamidis on renal function and its relationship to LV diastolic function is unclear. Purpose The purpose of this study was to investigate the relationship between changes in renal function after the acute phase of tafamidis administration and LV diastolic function at mid-term follow-up in patients with ATTR-CM. Methods We studied 56 patients with biopsy-proven ATTR-CM who were treated with tafamidis. All patients underwent blood examinations before and 45.6 ± 23.0 days after the acute phase of tafamidis administration. Echocardiography was performed before and 15.6 ± 9.8 months after the mid-term of tafamidis administration. The primary endpoint was defined as a composite of cardiovascular death or HF hospitalization for 5.0 years. Results Twelve patients had improved renal function as assessed by estimated glomerular filtration rate in the acute phase after tafamidis administration, while 44 patients deteriorated. In the group with improved renal function in the acute phase after tafamidis administration, pulsed-wave Doppler-derived early diastolic velocity from the septal mitral annulus (E’) and left atrial volume index (LAVI) tended to improve at mid-term follow-up compared to the non-improved group. (E’: 0.8 ± 1.7 cm/s vs. 0.2 ± 1.1 cm/s, p=0.127, LAVI: -8.7 ± 12.0 mL/m2 vs. 0.2 ± 16.8 mL/m2, p=0.093). Furthermore, Kaplan-Meier curve indicated that the occurrence of cardiovascular events for patients with improved renal function in the acute phase after tafamidis administration tended to be lower than those without (log-rank P=0.137). Conclusions The improvement of renal function in the acute phase after tafamidis administration was associated with the improvement of LV diastolic function at mid-term follow-up, leading to favorable outcome. Our findings may provide new insights for the management of patients with ATTR-CM.

Effect of stereotactic body radiation therapy on left ventricular diastole function in symptomatic patients with hypertrophic obstructive cardiomyopathy

Abstract Background We applied stereotactic body radiotherapy (SBRT) for the first time in the treatment of patients with hypertrophic obstructive cardiomyopathy (HOCM), and significant improvements in symptoms and diastolic function were observed after treatment. Objectives To evaluate the impact of SBRT on cardiac structure, function, and clinical indicators in patients with HOCM. Methods This study included 12 drug-refractory symptomatic HOCM patients (6 who underwent SBRT and 6 who received pharmacological treatment alone) and conducted a retrospective analysis of their clinical data. Transthoracic echocardiography was used to assess various ultrasound parameters, including interventricular septal thickness, left ventricular outflow tract diameter, peak pressure gradient and diastolic function before treatment and at 1, 3, and 6 months after treatment. Additionally, assessments were made for symptoms; laboratory test results (NT-proBNP, cTnT, CK-mb, and CRP); 6-minute walk test results; New York Heart Association (NYHA) functional classification; and Kansas score before and 6 months after treatment. Results HOCM patients showed significant improvement in mitral valve systolic anterior motion after SBRT. Compared to that at baseline, the interventricular septum thickness gradually decreased at 1, 3, and 6 months after treatment (-8.8%, -8.0%, -14.4%, respectively) (P<0.05). Compared to those in the drug group, the left ventricular diastolic function and structural parameters, including the interventricular septum thickness (mean change from baseline of -3 mm [95% CI: -5.2 to -0.8 mm] and 1.3 mm [95% CI: 0.5 to 2.2 mm]; P<0.05), and the LA GLS (change of 2.1% [-0.03% to 4.2%] and -0.9% [-3.1% to 1.3%]; P<0.05), were significantly improved in HOCM patients at 6 months posttreatment. Similarly, the clinical indicators, including KCCQ, increased from baseline (61 (range, 47.3-70) to 84 (range, 70-89.5) at 6 months posttreatment (P<0.05), and the 6-minute walk test score increased from 187 meters (range, 50-370) to 401 meters (range, 280-540) (P<0.05). Conclusion SBRT significantly improved left ventricular diastolic function and reduced interventricular septum thickness in HOCM patients. Symptoms, exercise capacity and clinical indicators improved after SBRT in HOCM patients.

Evaluating the effects of adrenalectomy and mineralocorticoid receptor antagonist on cardiac remodeling and diastolic function in patients with aldosterone-producing adenoma.

Cardiac remodeling and diastolic dysfunction in patients with aldosterone-producing adenomas (APA) can be improved after adrenalectomy. However, the effect of mineralocorticoid receptor antagonist (MRA) treatment remains unclear. The aim of this study is to evaluate the effect of MRA on cardiac remodeling and diastolic dysfunction in patients with PA. We prospectively enrolled patients with APA from 1993 to 2023, who either received medical treatment with MRAs or underwent adrenalectomy. Biochemical characteristics and echocardiographic findings were collected at baseline and one year after treatment. Propensity score matching was conducted based on baseline biochemical characteristics, left ventricular mass index (LVMI), and diastolic function. A total of 467 APA patients were enrolled in the study. After propensity score matching, 159 patients who underwent adrenalectomy were matched with 159 patients who received MRAs. After therapy, patients who received MRAs showed significant improvement in diastolic function after one year of treatment but not LVMI. Compared to the MRA group, the adrenalectomy group had greater improvement in systolic blood pressure, plasma aldosterone concentration, plasma renin activity, aldosterone-to-renin ratio, and LVMI. In multivariable regression analysis, pretreatment echocardiographic values were significantly associated with changes in both LVMI and E/e', while the treatment strategy showed a significant association with changes in LVMI. Thus, one year after therapy, both adrenalectomy and MRA are effective in improving diastolic function in patients with APA. However, adrenalectomy is more effective than MRA treatment in reversing cardiac remodeling in patients with APA.

Endovascular Treatment of Flow-Limiting Iliofemoral Stenosis Improves Left Ventricular Diastolic Function in Patients With HFpEF by Reducing Aortic Pulsatile Load.

Recent research indicates that there is a high prevalence of heart failure with preserved ejection fraction in patients with peripheral artery disease. We hypothesized that endovascular treatment (EVT) of flow-limiting peripheral stenosis improves left ventricular (LV) diastolic function. Thirty patients with symptomatic peripheral artery disease and heart failure with preserved ejection fraction according to Heart Failure Association-preserved ejection fraction score who were scheduled for EVT or angiography were investigated at baseline, the day after EVT (n=25) or angiography (control, n=5), and at 4 months follow-up. Peripheral hemodynamics were determined by the total peripheral resistance, common femoral artery flow, and ankle brachial index. Aortic function was measured by arterial compliance, augmentation index, and pulse wave velocity. Aortic pulsatile load was estimated as the characteristic impedance of the proximal aorta and the magnitude of wave reflection (reflection coefficient). LV mass index, LV mean wall thickness, and systolic and diastolic function were assessed using echocardiography. Patient-centered outcomes were treadmill walking distance and New York Heart Association class. After EVT, peripheral hemodynamics changed significantly with a decrease in total peripheral resistance and an increase in common femoral artery flow and ankle brachial index. Aortic function improved after EVT, with significantly reduced augmentation index and pulse wave velocity and increased compliance immediately and at follow-up, resulting in a reduction in aortic pulsatile load (characteristic impedance of the proximal aorta and reflection coefficient). Concurrently, LV diastolic function improved after EVT compared with control, acutely and at follow-up, with increased septal and lateral e´ velocities and decreased E/e´ and left atrial volume index. The LV mass index and LV mean wall thickness decreased at follow-up. The New York Heart Association class and treadmill walking distance improved post-EVT at follow-up. Augmentation index, pulse wave velocity, and arterial compliance were identified as independent contributors to E/e´. Endovascular treatment of flow-limiting iliofemoral stenosis reduces aortic pulsatile load and concurrently lowers total peripheral resistance. This beneficial effect is associated with an acute and sustained improvement of left ventricular diastolic function. URL: http://www.clinicaltrials.gov; Unique identifier: NCT02728479.

Mid-term clinical outcomes and cardiac function in patients receiving cardiac contractility modulation.

To describe the mid-term clinical and functional cardiac contractility modulation therapy (CCM) recipients in an urban population with heart failure. CCM is a non-excitatory electrical therapy for patients with systolic heart failure with NYHA class III symptoms and ejection fraction (EF) 25-45%. How CCM affects a broad range of clinical measures, including diastolic dysfunction (DD) and weight change, is unexplored. We reviewed 31 consecutive patients at our center who underwent CCM implant. NYHA class, hospitalizations, ejection fraction (EF), diastolic function, and weight were compared pre- and post-CCM implant. Mean age and follow-up time was 63 ± 10years and 1.4 ± 0.8years, respectively. Mean NYHA class improved by 0.97 functional classes (p < 0.001), and improvement occurred in 68% of patients. Mean annualized hospitalizations improved (0.8 ± 0.8 vs. 0.4 ± 1.0 hospitalizations/year, p = 0.048), and after exclusion of a single outlier, change in annualized days hospitalized also improved (total cohort 3.8 ± 4.7 vs. 3.7 ± 14.8days/year; p = 0.96; after exclusion, 3.8 ± 4.7 vs. 1.1 ± 1.9days/year, p < 0.001). Mean EF improved by 8% (p = 0.002), and among those with DD pre-CCM, mean DD improvement was 0.8 "grades" (p < 0.001). Mean weight change was 8.5 pounds lost, amounting to 4% of body weight (p = 0.002, p = 0.002, respectively), with 77% of patients having lost weight after CCM. Five patients (16%) experienced procedural complications; incidence skewed toward early implants. In an observational cohort, CCM therapy resulted in improvement in NYHA class, hospitalizations, systolic and diastolic function, and weight.

Effect of a polyherbal Unani formulation on left ventricular diastolic dysfunction in hypertensive patients- a randomized single blind placebo controlled clinical trial.

Diastolic dysfunction represents an important pathophysiological intermediate between hypertension and heart failure. In the last two decades, the prevalence of heart failure patients having normal or near normal ejection fraction (EF) has increased to around 60 %. It thus poses a great morbidity and mortality risk to the population. In view of present scenario of high prevalence, lack of evidence-based therapy, and limited clinical trials, this study aimed to evaluate how a Unani formulation affects the improvement of the left ventricular diastolic function. This clinical trial was set up as a randomized, placebo-controlled study involving 35 participants, with 18 individuals in the test group and 17 in the control group. Test group received 3.5 g of a polyherbal Unani formulation in capsule form along with 35 mL of an extract of Borago officinalis L. (Arq-e-Gaozaban), divided into two doses after meals. Meanwhile, the control group received a placebo in the same manner over an eight-week period. Follow-ups were conducted every 15days to assess both subjective and objective parameters in all participants. The test formulation shows significant improvement in dyspnea and diastolic function from baseline to the end of trial (p<0.05), slight improvement in palpitations (p>0.05) and highly significant improvement in easy fatigability (p=0.001) as compared to the control. The present study shows the effectiveness of the test drug in enhancing the diastolic function of left ventricle and alleviating other symptoms associated with ventricular diastolic dysfunction. Nevertheless, additional research with longer follow-up durations is necessary to clarify its efficacy and establish optimal treatment approaches for ventricular diastolic dysfunction in Unani medicine.

Efficacy and safety of Tongxin formula in the treatment of coronary microvascular disease: A randomized, double-blind, placebo-controlled clinical trial study

ObjectiveThe objective of this study was to evaluate the efficacy and safety of Tongxin Formula in the treatment of coronary microvascular disease. MethodsWe conducted a randomized, double-blind, placebo-controlled study simultaneously in two hospitals, consisting of 80 participants. Using a random number table, we assigned patients to the treatment and control groups. Patients in both groups received conventional Western medicine for coronary microvascular disease. In addition, those in the treatment group received Tongxin formula granules, while those in the control group received a placebo. The treatment course for both groups was three months, and the follow-up duration was six months. The primary efficacy indicators were coronary blood flow reserve and cardiovascular adverse events; the secondary efficacy indicators were the traditional Chinese medicine (TCM) syndrome score, the angina symptom score, the Seattle Angina Questionnaire (SAQ) score, left ventricular function, and adverse reactions. ResultsAfter treatment, patients in the treatment group showed significantly higher variation in the coronary flow reserve (CFR) levels (CFR >2) and improvement of diastolic function (peak filling rate, or PFR >2.5) than those in the control group (P < 0.05). After 6 months of follow-up, the incidence of cardiovascular events in the treatment group was significantly lower than that in the control group (P < 0.05). After 3 months of treatment and 6 months of follow-up, the total effective rates of TCM symptoms and angina symptoms, as well as the total SAQ standard scores, in the treatment group were higher than those in the control group (P < 0.05). There were no serious adverse reactions in either group before or after treatment, and there was no significant change (P > 0.05). ConclusionWe found that Tongxin Formula combined with conventional Western medicine can significantly improved the level of coronary blood flow reserve, reduced the occurrence of cardiovascular adverse events, improved the clinical symptoms of patients, and enhanced the quality of life of patients with coronary microvascular disease with favorable safety.

Hyperpolarized 13C and 31P MRS detects differences in cardiac energetics, metabolism, and function in obesity, and responses following treatment.

Obesity is associated with important changes in cardiac energetics and function, and an increased risk of adverse cardiovascular outcomes. Multi-nuclear MRS and MRI techniques have the potential to provide a comprehensive non-invasive assessment of cardiac metabolic perturbation in obesity. A rat model of obesity was created by high-fat diet feeding. This model was characterized using in vivo hyperpolarized [1-13C]pyruvate and [2-13C]pyruvate MRS, echocardiography and perfused heart 31P MRS. Two groups of obese rats were subsequently treated with either caloric restriction or the glucagon-like peptide-1 analogue/agonist liraglutide, prior to reassessment. The model recapitulated cardiovascular consequences of human obesity, including mild left ventricular hypertrophy, and diastolic, but not systolic, dysfunction. Hyperpolarized 13C and 31P MRS demonstrated that obesity was associated with reduced myocardial pyruvate dehydrogenase flux, altered cardiac tricarboxylic acid (TCA) cycle metabolism, and impaired myocardial energetic status (lower phosphocreatine to adenosine triphosphate ratio and impaired cardiac ΔG~ATP). Both caloric restriction and liraglutide treatment were associated with normalization of metabolic changes, alongside improvement in cardiac diastolic function. In this model of obesity, hyperpolarized 13C and 31P MRS demonstrated abnormalities in cardiac metabolism at multiple levels, including myocardial substrate selection, TCA cycle, and high-energy phosphorus metabolism. Metabolic changes were linked with impairment of diastolic function and were reversed in concert following either caloric restriction or liraglutide treatment. With hyperpolarized 13C and 31P techniques now available for human use, the findings support a role for multi-nuclear MRS in the development of new therapies for obesity.

Adjunctive therapy with an oral H2S donor provides additional therapeutic benefit beyond SGLT2 inhibition in cardiometabolic heart failure with preserved ejection fraction.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a potent therapy for heart failure with preserved ejection fraction (HFpEF). Hydrogen sulphide (H2S), a well-studied cardioprotective agent, could be beneficial in HFpEF. SGLT2i monotherapy and combination therapy involving an SGLT2i and H2S donor in two preclinical models of cardiometabolic HFpEF was investigated. Nine-week-old C57BL/6N mice received L-NAME and a 60% high fat diet for five weeks. Mice were then randomized to either control, SGLT2i monotherapy or SGLT2i and H2S donor, SG1002, for five additional weeks. Ten-week-old ZSF1 obese rats were randomized to control, SGLT2i or SGLT2i and SG1002 for 8 weeks. SG1002 monotherapy was investigated in additional animals. Cardiac function (echocardiography and haemodynamics), exercise capacity, glucose handling and multiorgan pathology were monitored during experimental protocols. SGLT2i treatment improved E/e' ratio and treadmill exercise in both models. Combination therapy afforded increases in cardiovascular sulphur bioavailability that coincided with improved left end-diastolic function (E/e' ratio), exercise capacity, metabolic state, cardiorenal fibrosis, and hepatic steatosis. Follow-up studies with SG1002 monotherapy revealed improvements in diastolic function, exercise capacity and multiorgan histopathology. SGLT2i monotherapy remediated pathological complications exhibited by two well-established HFpEF models. Adjunctive H2S therapy resulted in further improvements of cardiometabolic perturbations beyond SGLT2i monotherapy. Follow-up SG1002 monotherapy studies inferred an improved phenotype with combination therapy beyond either monotherapy. These data demonstrate the differing effects of SGLT2i and H2S therapy while also revealing the superior efficacy of the combination therapy in cardiometabolic HFpEF.

Early reverse remodeling by echocardiography after transcatheter aortic valve implantation.

Oslo University Hospital is a tertiary center conducting a significant number of transcatheter aortic valve implantation (TAVI) procedures per year. In this follow-up MediPace study, we aimed to investigate early echocardiographic changes in systolic and diastolic functions after TAVI in these patients. All patients enrolled in the previous study were contacted 3 months after TAVI for echocardiographic evaluation. Detailed echocardiography was performed 3.5±1.6 months after TAVI, and compared with baseline evaluations. A total of 101 patients were analyzed. Mean age was 80.1±6.8 years and 40% of the patients were female. We observed a significant improvement in global longitudinal strain (GLS) (pre-TAVI -16.8±4.1%, post-TAVI -17.8±3.6%, p <.001), with no notable change in LVEF. More than half of the patients (52%) experienced a significant reverse remodeling with ≥10% decrease in left ventricular mass index (LVMi) following TAVI (pre-TAVI 123.6±32.1vs. 109.7±28.9g/m2 post-TAVI, p <.001). Pre-TAVI LVMi was a positive predictor, whereas history of HT was a negative predictor of LVMi reduction. There was no significant improvement in diastolic function following TAVI. Highest degree of paravalvular leakage was mild to moderate and was observed in only 2%. A significant improvement in GLS and LVMi was found following TAVI. History of hypertension and baseline LVMi were predictors of LVMi change. There was no notable change in diastolic function, including left atrial strain.

The effect of bachmann bundle pacing on diastolic function in patients with non-obstructive HCM

Abstract Background and Objective Patients with non-obstructive HCM (nHCM) have advanced diastolic dysfunction and atrial remodeling, leading to increased heart failure hospitalisations. The objective of this study was to evaluate the role of Bachmann bundle pacing (BBP) in diastolic filling compared to right atrial appendage pacing (RAAP). Methods Forty patients with symptomatic nHCM and normal LV function were prospectively enrolled from January 2021 to June 2023. Inclusion criteria included electrocardiographic evidence of inter-atrial delay, E/e’ &amp;gt; 15, and an indication for ICD implantation. BBP was attempted in twenty patients, others underwent RAAP. A Biotronik Selectra 3D 40-S sheath was used for BBP in patients in whom initial lead implantation was unsuccessful. BBP was defined based on P-wave morphology and fluoroscopic lead position. The RV lead was implanted in the RV apex in all patients and the AV delay was optimized based on diastolic filling period and E/e’. Devices were programmed in DDD mode. During follow up, diastolic function, functional capacity, atrial fibrillation, and heart failure hospitalisations were assessed in both groups. Results Among the forty patients (age 48.2+7.8 yrs, males 75%, ESC-SCD Risk 4.3+0.6%), the baseline P wave duration, E/A, E/e’ were 138.4+16.4 ms, 2.5+0.5, and 17.5+2.4, respectively. Six patients (15%) had a history of paroxysmal AF (3 each in BBP and RAAP groups). Of the 16 patients (80%) who underwent successful BBP, the Selectra 3D 40-S sheath was used in 8 patients (Figure 1, Panel A). During BBP, a bachmann bundle potential was recorded in 7 of 16 patients (43.8%) (Figure 1, Panel C). The pacing threshold (1.5+0.5@0.4ms vs. 0.9+0.3@0.4ms, p=0.026) was higher and the atrial sensing (1.8+0.4 vs. 3.3+0.6, p=0.002) was lower in the BBP group compared to the RAAP group at 4 weeks and 6 months of follow up. There was an acute rise in threshold (2.1@0.4 ms) in 1 BBP patient at 4 weeks of follow up. Patients in the BBP group had a reduction in P wave duration compared to the patients in the RAAP group (-22.5 + 5.4 vs. +5.6 + 3.2 ms, p&amp;lt;0.001). During follow up (11.4 + 3.4 months), there was a significant improvement in diastolic function (E/e’), functional capacity (NYHA Class) and reduction in NT-proBNP in the BBB group compared to the RAAP group (Figure 1). The percentage of atrial pacing was similar in both groups (BBP 73.2 + 7.8 vs. RAAP 78.5 + 9.1 %, p=0.219). The risk of atrial fibrillation/tachycardia (12.5% vs. 35.0%, p=0.022) and heart failure hospitalisations (6.3% vs. 20%, p=0.042) was lower in the BBP group compared with RAAP during follow up. Conclusions BBP is safe and effective in improving diastolic function, functional capacity and heart failure hospitalizations in patients with nHCM.BBP Pacing using Selectra 3D 40-S SheathChange in E/e', NYHA, and NT-pro BNP

#1755 Cardio-protective effect of soy proteins during long-term consumption of Cynomolgus Monkeys high-saline diet

Abstract Background and Aims High salt intake is accompanied by the development of cardiovascular disorders, not always associated with an increase in blood pressure (BP). Recently, it has been found that the introduction of soy protein into the diet can have some nephroprotective and cardioprotective effects in chronic kidney disease. Considering the cardioprotective effect of soy proteins in chronic kidney disease, the question arose about the possibility of using soy proteins to neutralize the damaging effect of a high-salt diet on the cardiovascular system. This work aims to study the effect of long-term use of a diet high in NaCl and soy protein on myocardial remodeling in monkeys. Method The study was performed on male Macaca fascicularis. The animals were divided into three groups (6 animals each), comparable in weight and age (6-8 years, body weight - 5.15-9.7 kg). The control group received a standard diet (2 g NaCl/kg feed). The second was a high salt diet (8 g NaCl/kg feed), and the third was a high salt diet and SUPRO760 soy protein (200 g/kg feed). Echocardiography (EchoCG), registration of BP and heart rate were performed at baseline, after 4 and 12 months. EchoCG was performed with a sector transducer with a frequency of 3–5 MHz on the Chison SonoTouch 60 ultrasound system (China). EchoCG was performed in B_mode (two-dimensional scanning), M_mode (one-dimensional scanning), as well as in pulse and tissue Doppler modes. Statistical analysis was performed using parametric statistics: mixed ANOVA in comparing data from 3 study groups (with post hoc analysis using Tukey criterion) and single factor variance analysis for related samples in studying the dynamics of one or another index in each group during the 12-month follow-up. Differences were considered significant at p &amp;lt; 0.05. Results In animals of all three groups for 12 months, blood pressure (BPsis-109±10.09, BPdias – 60 ± 7.42 mm Hg) and heart rate (77 ± 12.61 min-1) did not change significantly (p&amp;gt;0. 05). However, in macaques on a high-salt diet, deterioration in left ventricular (LV) systolic and diastolic function was noted by the end of the study. Macaques of this group had a decrease in the LV shortening fraction (27.9±2.69%) and an increase in the thickness of the posterior wall of the LV in systole (0.69±0.039 cm), LV mass (19.60±2.83 g), compared with animals additionally receiving soy proteins (34.9±6.57%; 0.57 0.0559 cm; 14.86±2.94 g, respectively; all p &amp;lt; 0.05). In addition, the monkeys receiving soy isolate did not differ from the control in these parameters. By the time the study was completed, the animals in this group had significantly increased the magnitude of systolic excursion of the mitral annulus plane, and signs of improvement in LV diastolic function appeared in the form of an increase in the maximum rate of excursion of the mitral valve fibrous annulus in early diastole, as well as a decrease in the E/e' ratio. The thickness of the interventricular septum also decreased (0.42±0.04 cm; in the high-salt group - 0.51±0.08 cm), which can be interpreted as a sign of positive myocardial remodeling. Conclusion Thus, high salt intake leads to adverse structural and functional disorders of the heart in cynomolgus monkeys, not associated with an increase in blood pressure. The inclusion of soy isolate in the diet reduces the negative effects of a high-salt diet on the cardiovascular system.

Therapeutic potential of hiPSC-derived cardiomyocytes for Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) results in progressive and incurable cardiomyopathy, leading to significant morbidity and mortality due to heart failure. There is currently no effective cure for DMD that can correct the genetic defects and compensate for the lack of dystrophin. Therefore, the therapeutic strategies that focus on the transplantation of induced pluripotent stem cells (iPSCs) derived cardiomyocytes are promising options, and remain to be investigated to which extent they can restrain the cardiomyocyte loss phenotype and improve cardiac function. There has been significant progress in the differentiation of cardiomyocytes (CMs) from hiPSCs (human iPSCs). Three hiPSC lines: AICS-0011, 029 iPS clone 4-PCBC, and PCBC16iPS were investigated based on previously published culture and differentiation methods. We will inject differentiated CMs into the heart of Mdx mice that are mutated or deficient for NOD-scid, IL2Rg to allow for xenotransplantation engraftment. Having confirmed the effcient differentiation of CMs from all three hiPSC lines, the next step will be to transplant CMs. The engraftment rate after transplantation will be quantified by IHC staining for human lamin A/C and the relative level of genomic human DNA from isolated hearts. Correction of dystrophin expression will be measured via IHC for dystrophin. Echocardiography will be performed to measure improvement in cardiac systolic or diastolic function. If therapeutic transplantation of hiPSC-CMs is possible, it could improve the survival of DMD patients. This project was supported by RMM091621DS008, NIH155993, and NIH160665. 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.

COMPARISON OF CARDIAC STRUCTURAL AND FUNCTIONAL CHANGES BETWEEN SURGERY AND MEDICATION TREATMENT IN PATIENTS WITH PRIMARY ALDOSTERONISM BASED ON ECHOCARDIOGRAPHY

Objective: Conducted a systematic meta-analysis on the changes in follow-up parameters of echocardiography in patients with primary aldosteronism after surgery and drug treatment, in order to explore their differences. Design and method: We conducted the PubMed, Embase, and Cochrane library databases for English full-text articles on the follow-up study of echocardiography parameters in PA patients before and after surgery and drug treatment published from its establishment until June 1, 2023,Perform meta-analysis on the included studies using RevMan software. Results: A total of 515 PA patients (&gt;18 years old) were included in 4 studies, including the surgical group (n=303) and the medication group (n=212), 2 short-term follow-up studies (average follow-up time of 1 year), and 2 long-term follow-up studies (average follow-up time of 3.7 years). Surgery treatment had better performance in improving cardiac contractile function, The main manifestation is the reversal of left ventricular hypertrophy (LVMI: M=-2.6, p=0.047), while there is no significant improvement in cardiac diastolic function (E/A: M=+0.06, p=0.51); In long-term follow-up studies, surgery and medical treatment still showed significant benefits in reducing blood pressure (surgical group: -14 ± 6 mm Hg/-9 ± 10 mm Hg, p&lt;0.001; drug group: -10 ± 12mmHg/-11 ± 9mmHg, p&lt;0.001). Interestingly, the surgical group and drug group did not show better blood pressure control effects than short-term follow-up (p=0.56), Surgery (LVMI: M=-12.6, p=0.01)and medication (LVMI: M=-11.9, p=0.01])can significantly improve left ventricular hypertrophy in patients, with no significant difference (P=0.143). Although surgery (E/A: M=+0.14, p=0.125) and medication (E/A: M=+0.09, p=0.2) can numerically improve diastolic function, there is no statistically significant difference. Conclusions: Both medication and surgical treatment can reverse the damage to the heart structure and function in PA patients. In the short term, surgical treatment has a more significant reversal of cardiac function, especially in left ventricular hypertrophy, but in the long term, there is no significant difference between medication and surgical treatment.

Cholinergic Stimulation Exerts Cardioprotective Effects and Alleviates Renal Inflammatory Responses after Acute Myocardial Infarction in Spontaneous Hypertensive Rats (SHRs).

In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Adult male SHRs were randomized into three experimental groups: sham-operated; AMI + Veh (infarcted, treated with vehicle); and AMI + PY (infarcted, treated with the cholinesterase inhibitor, pyridostigmine bromide (PY)-40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. The clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Seven days post-surgery, the AMI + PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI + Veh group. Furthermore, there was a notable downregulation in pro-inflammatory gene expression and an upregulation in anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers, indicative of subclinical kidney injury. Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

Influence of dapagliflozin on cardiovascular remodeling in hypertensive patients with accompanying type 2 diabetes

Aim. To compare the results of 12-week treatment of patients with stage II hypertension (HTN) with accompanying diabetes mellitus (DM) type 2 between the combination of metformin + dapagliflozin and metformin monotherapy by studying changes in the elastic properties of the common carotid arteries (CCA), echocardiographic indicators, 24-hour ambulatory blood pressure monitoring (ABPM) and laboratory parameters of lipid and carbohydrate metabolism. Materials and methods. 24 patients with stage II HTN with type 2 DM were involved in the study, the average age was 60.4 years, 50 % – men. Patients in the first group were randomized to receive metformin, and the second group – to receive a combination of metformin and dapagliflozin. At inclusion and after 3 months of treatment, basic anthropometric data, laboratory indicators of lipid and carbohydrate metabolism, ABPM, echocardiography, and indicators of CCA local stiffness were studied. Statistical analysis was performed, the probability of differences is at the level of p &lt; 0.05. Results. In both observation groups, there was a comparable decrease in SCORE 2-Diabetes range, glucose and glycated hemoglobin, total cholesterol, LDL cholesterol, average daily systolic blood pressure (SBP), daily SBP load, day and night pulse BP, as well as an increase in speed systolic movement of the lateral fibrous ring of the mitral valve (S lat). Only in the metformin + dapagliflozin group a decrease in the adipose tissue level, the average daily diastolic blood pressure (DBP), the burden of DBP, the size of the left atrium and right ventricle, an increase in the movement speeds of the medial (e’med), lateral (e’lat) ring of the mitral and of the tricuspid (e’tk) valve in the period of early diastolic filling of the ventricles, velocities of systolic movement of the medial fibrous ring of the mitral (S med) and tricuspid (S tk) valves, a decrease in the ratio E/e’, and an improvement in the elastic properties of general carotid arteries were observed. Conclusions. In persons with HTN stage II with DM type 2 the addition of dapagliflozin to the treatment regimen was associated with better control of blood pressure, improvement of diastolic function and longitudinal contractility of the left ventricle, elastic properties of CCA.

Concurrent Resistance and Cardiorespiratory Training in Patients with Hypertrophic Cardiomyopathy: A Pilot Study.

Background: Exercise training in patients with HCM has evidenced benefits on functional capacity, cardiac function, and a reversion of adverse cardiac remodeling. The objective of this study was to assess the effect of a concurrent resistance and cardiorespiratory training program on functional capacity, biochemical parameters, and echocardiographic variables in a pilot group. Methods: Two HCM patients were evaluated before and after 12 weeks of individualized concurrent training with two sessions/week. Pre- and post-training data were compared for each patient. Evaluations included a cardiopulmonary exercise test (CPET), body composition, echocardiography, electrocardiography, and blood analysis. Results: Training promoted an increase in functional capacity (+4 mL·kg-1·min-1), ventilatory thresholds, and other CPET-derived variables associated with a better prognosis and long-term survival. Muscular mass was augmented (0.8 and 1.2 kg), along with a mean increase of 62% in upper and lower body strength. Echocardiographic features demonstrated the maintenance of cardiac function with signs of positive left ventricular remodeling and an improvement in diastolic function. Blood analyses, including cardiac troponins and NT-proBNP, displayed uneven changes in each patient, but the values fell into normal ranges in both cases. Conclusions: The available data suggest a positive effect of concurrent resistance and cardiorespiratory training on patients' functional capacity and cardiac function that may improve their functional class, quality of life, and long-term prognosis. The replication of this protocol in a larger cohort of patients is warranted to confirm these preliminary results.

Heart failure with preserved ejection fraction: A short review of diagnosis and management

Around 64 million persons in the world have heart failure (HF). HF patients with left ventricle ejection fraction (LVEF) of ≥50% are classified as having HF with preserved ejection fraction (HFpEF). It is estimated that about fifty percent of all HF is HFpEF. Our aim was to provide evidence of contemporary data regarding diagnosis and management of HFpEF. We conducted literature search through online search such as Google Scholar and PubMed Central (PMC), focusing on diagnosis and management of HFpEF. Several criteria exist for the diagnosis of HFpEF, including EF 50%, evidence of diastolic dysfunction, elevated brain natriuretic peptide. High (≥15) or intermediate (9–14) E/eʹ index indicates the likelihood of HFpEF. SGLT2I decrease E/eʹ, indicating improvement of LV diastolic function as mentioned in several studies. Treatment duration to achieve this effect spans from 3 months to 1 year. SGLT2I have positive effect on echocardiographic parameter HFpEF patients. In the researches included in the review, E/eʹ was mainly used as primary end point.