Higher Left Ventricular Ejection Fraction Research Articles

Clinical and instrumental factors associated with sinus rhythm maintenance following direct current cardioversion of late persistent non-valvular atrial fibrillation at 6-months follow-up

Abstract Purpose To study the clinical and instrumental factors, associated with sinus rhythm (SR) maintenance following direct current cardioversion (DCCV) in patients with late persistent non-valvular atrial fibrillation (AF) at 6-months follow-up. Methods The cohort single-center study analyzed clinical and instrumental data from 59 late persistent AF patients (with duration of its episode ≥90 days [up to 12 months]), who underwent an elective DCCV. At 6-months follow-up, 32 (54 %%) patients succeeded to maintain SR, in contrast to 27 (46 %) patients with a failure to its maintenance. Results The univariate logistic regression analysis revealed, that the absence of heart failure (HF) stage C (i.e., the presence of its stage B), the higher left ventricular ejection fraction (LVEF) (by transthoracic echocardiography [TTE]), left atrial appendage flow velocity (LAAFV) >40 cm/s and the freedom from left atrial spontaneous echo contrast (LASEC) (by transesophageal echocardiography), ‒ all were associated with the higher chance to maintain SR at 6-months follow-up (Figure). At the same time, the higher baseline left atrial dimension (LAD) and more advanced pulmonary hypertension (PH) (by TTE) were associated with the failure of its maintenance to be more probable (Figure). At multivariate analysis, the following predictors of SR maintenance after DCCV at 6-months follow-up were identified: higher LVEF (OR 1,07 (95 % CI 1,01-1,13); р=0,021); LAAFV >40 cm/s (OR 4,33 (95 % CI 1,06-17,78); р=0,042), and less advanced PH (OR 0,24 (95% CI 0,06-0,93); р=0,038). Conclusion Better LV systolic function, LAAFV >40 cm/s and less advanced PH were the predictors of SR maintenance following DCCV in patients with late persistent (with duration of its episode ≥90 days) non-valvular AF at 6-months follow-up.

Lead break during extraction - predisposing factors and impact on procedure complexity and outcome on the basis of analysis of 3825 procedures

Abstract Background There are no reports describing lead break (LB) during transvenous lead extraction (TLE). Our aim was to compare the effectiveness of different approaches and tools used for LB removal during 127 procedures. Methods Retrospective analysis of 3825 consecutive TLEs using mechanical sheaths. Results Fracture of the lead defined as LB with a long lead fragment (LF) occurred in 2.48%, LB with a short LF in 1.20%, LB with the tip of the lead in 1.78% and LB with loss of a free-floating LF in 0.57% of cases. In total, extractions with LB occurred in 6.04%. In cases in which lead remnant was equivalent to a lead fragment (more than the lead tip only) there was a 50.31% chance of removing the LF in its entirety and an 18.41% chance of significantly reducing its length (to less than 4 cm). Risk factors for LB are similar to those for major complications and increased procedure complexity: long lead dwell time [OR=1.018], higher LV ejection fraction, multiple previous CIED-related procedures and extraction of passive fixation leads. A superior approach was the most popular (75.59%), femoral (15.75%) and combined (8.66%) approaches were the least common. Broken lead fragments (BLFs) were removed in their entirety in 63.78% and BLF length was significantly reduced (to less than 4 cm) in 24.41%. The best results were achieved when BLFs were longer (>4 cm) (66.67%), either free-floating or in the pulmonary circulation (68.42%) but not in cases of short BLFs (20.0%). Complete procedural success was achieved in 70.87% of procedures, the lead tip retained in the heart wall and short BLFs were found in 25.98%, whereas BLFs > 4 cm were left in place in 3.15% of procedures only. There was no relationship between approach in lead remnant removal and long-term mortality. All forms of LB were associated with increased procedure complexity and major complications (9.96% and 1.53%). There was no procedure-related death among such patients and LB did not affect survival after TLE. Conclusions 1. LB during TLE occurs in 6.04% of procedures and it increases procedure complexity and risk of major complications. Thus, the possibility of LB should be taken into account when planning lead extraction strategy and training. 2. Effectiveness of fractured lead removal is satisfactory. 3.Risk factors for lead fracture are implant duration (16.27 years on average), ventricular leads (71.65%), passive fixation leads (97.63%) and pacemaker leads (92.13%), but not ICD leads (only 7.87% of lead fractures). 4. Broken lead removal using a coronary sinus access sheath as a "subclavian workstation" for continuation of dilatation with conventional tools deserves attention.

Application of intensive management of risk awareness combined with cardiac rehabilitation nursing in elderly patients with acute myocardial infarction and heart failure.

The aim of this study is to assess the impact of intensive risk awareness management along with cardiac rehabilitation nursing in elderly patients with acute myocardial infarction and heart failure. We selected 101 elderly patients with acute myocardial infarction and heart aging treated from January 2022 to March 2023. They were divided into control and observation groups based on hospitalization numbers. The control group (n = 50) received routine nursing, while the observation group (n = 51) received intensive risk awareness management and cardiac rehabilitation nursing. We compared medication possession ratio (MPR), cardiac function, self-care ability scale scores, quality-of-life, incidents, and satisfaction between the 2 groups. Before intervention, there was no significant difference in MPR values between the 2 groups (P > .05). After intervention, MPR values increased in both groups, with a greater increase in the observation group (P < .05). Cardiac function showed no significant difference before intervention (P > .05), but after intervention, the observation group had lower left ventricular end-systolic and diastolic diameters and higher left ventricular ejection fraction compared to the control group (P < .05). Self-care skills, health knowledge, self-responsibility, and self-concept scores improved in both groups after intervention, with higher scores in the observation group (P < .05). The observation group had higher scores in various quality-of-life domains (P < .05). The total incidence of adverse events was lower in the observation group (5.88%) compared to the control group (20.00%) (P < .05). Patient satisfaction was significantly higher in the observation group (96.08%) than in the control group (84.00%) (P < .05). Intensive risk awareness management combined with cardiac rehabilitation nursing in elderly patients with acute myocardial infarction and heart aging can enhance medication compliance, improve quality-of-life, enhance self-care abilities, boost cardiac function, reduce incidents, and increase patient satisfaction.

Finerenone in patients with heart failure with mildly reduced or preserved ejection fraction: Rationale and design of the FINEARTS-HF trial.

Steroidal mineralocorticoid receptor antagonists (MRAs), spironolactone and eplerenone, are strongly recommended in the treatment of patients with chronic heart failure (HF) with reduced left ventricular ejection fraction (LVEF), but the balance of efficacy and safety in those with higher LVEF has not been well established. Broad use of steroidal MRAs has further been limited in part due to safety concerns around risks of hyperkalaemia, gynecomastia, and kidney dysfunction. These risks may be mitigated by the unique pharmacological properties of the non-steroidal MRA finerenone. The FINEARTS-HF trial is designed to evaluate the long-term efficacy and safety of the selective non-steroidal MRA finerenone among patients with HF with mildly reduced or preserved ejection fraction. FINEARTS-HF is a global, multicentre, event-driven randomized trial evaluating oral finerenone versus matching placebo in symptomatic patients with HF with LVEF ≥40%. Adults (≥40 years) with HF with New York Heart Association class II-IV symptoms, LVEF ≥40%, evidence of structural heart disease, and diuretic use for at least the previous 30 days were eligible. All patients required elevated natriuretic peptide levels: for patients in sinus rhythm, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥300 pg/ml (or B-type natriuretic peptide [BNP] ≥100 pg/ml) were required, measured within 30 days (in those without a recent worsening HF event) or within 90 days (in those with a recent worsening HF event). Qualifying levels of NT-proBNP or BNP were tripled if a patient was in atrial fibrillation at screening. Estimated glomerular filtration rate <25 ml/min/1.73 m2 or serum potassium >5.0 mmol/L were key exclusion criteria. Patients were enrolled irrespective of clinical care setting (whether hospitalized, recently hospitalized, or ambulatory). The primary endpoint is the composite of cardiovascular death and total (first and recurrent) HF events. The trial started on 14 September 2020 and has validly randomized 6001 participants across 37 countries. Approximately 2375 total primary composite events are targeted. The FINEARTS-HF trial will determine the efficacy and safety of the non-steroidal MRA finerenone in a broad population of hospitalized and ambulatory patients with HF with mildly reduced or preserved ejection fraction. ClinicalTrials.gov NCT04435626 and EudraCT 2020-000306-29.

Recovery of left ventricular systolic function in peripartum cardiomyopathy: an observational study from rural Tanzania

BackgroundThe aim of this study was to evaluate the recovery rate of the left ventricular systolic function of women diagnosed with peripartum cardiomyopathy receiving specialized care in rural Tanzania.MethodsIn this observational study, women diagnosed with peripartum cardiomyopathy at a referral center in rural Tanzania between December 2015 and September 2021 were included. Women diagnosed between February and September 2021 were followed prospectively, those diagnosed between December 2015 and January 2021 were tracked back for a follow-up echocardiography. All participants received a clinical examination, a comprehensive echocardiogram, and a prescription of guideline-directed medical therapy. The primary outcome was recovery of the left ventricular systolic function (left ventricular ejection fraction > 50%).ResultsMedian age of the 110 participants was 28.5 years (range 17–45). At enrolment, 49 (45%) participants were already on cardiac medication, 50 (45%) had severe eccentric hypertrophy of the left ventricle, and the median left ventricular ejection fraction was 30% (range 15–46). After a median follow-up of 8.98 months (IQR 5.72–29.37), 61 (55%) participants were still on cardiac medication. Full recovery of the left ventricular systolic function was diagnosed in 76 (69%, 95% CI 59.6–77.6%) participants. In the multivariate analysis, a higher left ventricular ejection fraction at baseline was positively associated with full recovery (each 5% increase; OR 1.7, 95% CI 1.10–2.62, p = 0.012), while higher age was inversely associated (each 10 years increase; OR 0.40, 95% CI 0.19–0.82, p = 0.012).ConclusionLeft ventricular systolic function recovered completely in 69% of study participants with peripartum cardiomyopathy from rural Tanzania under specialized care.

Association of Sacubitril/Valsartan versus Valsartan with Blood Pressure Changes, and Symptomatic Hypotension: The PARAGLIDE-HF Trial

In PARAGLIDE-HF, among patients with ejection fraction (EF) >40%, stabilized after worsening heart failure (WHF), sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared to valsartan alone, despite more symptomatic hypotension (SH). Concern over SH may be limiting use of sacubitril/valsartan in appropriate patients. We characterized patients by the occurrence of SH (investigator-reported) after randomization to either sacubitril/valsartan or valsartan. A key trial inclusion criterion was systolic blood pressure (SBP) ≥100 mmHg for the preceding 6 hours and no SH. We also compared outcomes based on baseline SBP stratified by the median blood pressure. The primary endpoint was time-averaged proportional change in NT-proBNP from baseline through Weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: a) cardiovascular death, b) HF hospitalizations, c) urgent HF visits, and d) change in NT-proBNP. Among 466 randomized patients, 92 (19.7%) experienced SH (sacubitril/valsartan, N=56 [24.0%]; valsartan, N=36 [15.5%], p=0.020). The median time to the first SH event was similar between treatment arms (18 days vs. 15 days, respectively, p=0.42) as was the proportion of first SH events classified as "serious" by investigators. Patients who experienced SH with sacubitril/valsartan were more likely to be White (OR 1.87 [95%CI: 0.31, 11.15]), to have a lower baseline SBP (per 10mmHg increase OR 0.68 [95%CI: 0.55, 0.85]), or to have a left ventricular ejection fraction (LVEF) of >60% (OR 2.21 [95%CI: 1.05, 4.65]). Time-averaged change in NT-proBNP did not differ between patients with baseline SBP ≥128 mmHg vs. SBP<128mmHg (interaction p=0.43). The composite hierarchical outcome for sacubitril/valsartan in patients with baseline SBP≥128mmHg had a win ratio of 1.34 ([95%CI: 0.91, 1.99], p=0.096) vs SBP<128mmHg with a win ratio of 1.09 ([95%CI: 0.73, 1.66], p=0.62; interaction p value=0.42). Among patients with LVEF>40% stabilized after WHF, incident SH was more common with sacubitril/valsartan compared with valsartan. SH was associated with lower baseline SBP, White race, and higher LVEF. Treatment benefits with sacubitril/valsartan may be more pronounced in patients with higher baseline SBP and lower LVEF (≤ 60%). (Funded by Novartis Pharmaceutical Corporation; ClinicalTrials.gov number, NCT03988634.) ABBREVIATIONS: : HFpEF, heart failure with preserved ejection fraction; HFmrEF, heart failure with mildly reduced ejection fraction; HFrEF, heart failure with reduced ejection fraction; LVEF, left ventricular ejection fraction; NT-proBNP, amino terminal-pro b-type natriuretic peptide; SBP, systolic blood pressure; WHF, worsening heart failure.

Lead Break during Extraction: Predisposing Factors and Impact on Procedure Complexity and Outcome: Analysis of 3825 Procedures.

Background: Currently, there are no reports describing lead break (LB) during transvenous lead extraction (TLE). Methods: This study conducted a retrospective analysis of 3825 consecutive TLEs using mechanical sheaths. Results: Fracture of the lead, defined as LB, with a long lead fragment (LF) occurred in 2.48%, LB with a short LF in 1.20%, LB with the tip of the lead in 1.78%, and LB with loss of a free-floating LF in 0.57% of cases. In total, extractions with LB occurred in 6.04% of the cases studied. In cases in which the lead remnant comprises more than the tip only, there was a 50.31% chance of removing the lead fragment in its entirety and an 18.41% chance of significantly reducing its length (to less than 4 cm). Risk factors for LB are similar to those for major complications and increased procedure complexity, including long lead dwell time [OR = 1.018], a higher LV ejection fraction, multiple previous CIED-related procedures, and the extraction of passive fixation leads. The LECOM and LED scores also exhibit a high predictive value. All forms of LB were associated with increased procedure complexity and major complications (9.96 vs. 1.53%). There was no incidence of procedure-related death among such patients, and LB did not affect the survival statistics after TLE. Conclusions: LB during TLE occurs in 6.04% of procedures, and this predictable difficulty increases procedure complexity and the risk of major complications. Thus, the possibility of LB should be taken into account when planning the lead extraction strategy and its associated training.

Biventricular function in preterm infants with patent ductus arteriosus ligation: A three-dimensional echocardiographic study.

The detailed hemodynamics after patent ductus arteriosus (PDA) ligation in preterm infants remain unknown. We aimed to clarify the effect of surgical ligation on left ventricular (LV) and right ventricular (RV) volume and function. Echocardiography was performed in 41 preterm infants (median gestational age: 25 weeks) before and after PDA ligation. Global longitudinal strain was determined using three-dimensional speckle-tracking echocardiography. These values were compared with those in 36 preterm infants without PDA (non-PDA). Preoperatively, the PDA group had greater end-diastolic volume (EDV) and cardiac output (CO) in both ventricles, a higher LV ejection fraction (LVEF) (53% vs 44%) and LV global longitudinal strain, and a lower RVEF (47% vs 52%) than the non-PDA group. At 4-8 h postoperatively, the two groups had a similar LVEDV and RVEDV. However, the PDA group had a lower EF and CO in both ventricles than the non-PDA group. At 24-48 h postoperatively, the RVEF was increased, but the LVEF remained decreased, and LVCO was increased. PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery. Three-dimensional echocardiography may be beneficial to understand the status of both ventricles. Preterm infants are at high risk of hemodynamic compromise following a sudden change in loading conditions after PDA ligation. Three-dimensional echocardiography enables quantitative and serial evaluation of ventricular function and volume in preterm infants with PDA. PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery.

A follow-up program in patients after hospitalization for heart failure: long-term health related quality of life and associated factors.

The well-being of individuals with chronic heart failure (HF) is significantly influenced by their health-related quality of life (HRQoL), which serves as a crucial measure indicating how HF affects their daily activities. Monitoring programs aimed at reducing the number of hospitalizations and improving functional conditions are currently being offered to patients with chronic HF. To examine the long-term health-related quality of life changes in patients with heart failure enrolled in a follow-up program after hospitalization and to evaluate the factors associated with quality of life of patients with heart failure. This prospective study was conducted between 2019 and 2020 at the Department of Cardiology of Lithuanian University of Health Sciences. Patients were divided into two groups: Group I consisted of 71 patients (60.2%) where the Minnesota Living with Heart Failure Questionnaire (MLHFQ) score decreased by more than 10 points at 4th visit if compared to the 1st one; and Group II consisted of 47 patients (39.8%) where the MLHFQ score remained unchanged or increased by less than 10 points at the 4th visit if compared to the 1st visit. Statistically significant differences were observed between groups. In Group II, a history of myocardial infarction was more frequent (p = 0.038), and there was a significantly higher occurrence of significant coronary artery disease (p = 0.006). Laboratory parameters indicating liver function exhibited statistically significant deterioration among patients in Group II. Specifically, AST (p = 0.050), ALT (p = 0.010), and GGT (p = 0.031) levels significantly increased. Upon analyzing the echocardiographic data, a statistically significant difference was found between the groups in relation to the left ventricular ejection fraction (LVEF) (p = 0.043) and TAPSE (p = 0.031). An analysis of changes in dimensions related to QoL was conducted during the long-term follow-up program, which revealed statistically significant differences between groups in overall changes based on the MLHFQ (p < 0.001). This difference was also observed across all dimensions, including the emotional, physical, and social aspects (p < 0.001). Patients who had a higher LVEF at baseline, as well as those with an etiology of ischemic heart disease (IHD), better liver function, and fewer manifestations of edema, demonstrated a statistically significant improvement in their quality of life throughout the course of the patient monitoring program.

Achieved dose and treatment discontinuation of candesartan in men and women with chronic heart failure: data from CHARM.

Angiotensin receptor blockers have been shown to reduce heart failure hospitalization and cardiovascular mortality in men and women with heart failure with reduced ejection fraction (HFrEF). It is unknown whether there are differences between men and women in achieved dose and treatment discontinuation due to adverse events of candesartan. We conducted a post hoc analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. A total of 3172 men and 1106 women with HFrEF [left ventricular ejection fraction (LVEF)≤40%] in New York Heart Association class II-IV were randomized to candesartan or placebo. Every 2weeks, patients were up-titrated from 4 or 8, to16, to 32mg once daily, unless a higher dose was contraindicated or not tolerated. Women were older (66 vs. 64years), had a higher LVEF (29.9% vs. 28.6%), and had more hypertension (54% vs. 47%) than men. The mean achieved dose of candesartan was 21.5±12.6mg in men and 20.7±12.9mg in women (P=0.19). In both the candesartan and placebo groups, cardiovascular death and heart failure hospitalizations were higher in men and women who achieved lower dose levels. Event rates for achieved dose levels of 0, 4 or 8, 16, and 32mg candesartan were 20.8, 17.2, 14.0, and 10.1 per 100 person-years in men, respectively, and 23.6, 13.7, 14.0, and 9.1 per 100 person-years in women, respectively. In each of the achieved dose levels, there was no sex difference in the proportion of patients with an event, neither in the candesartan group nor in the placebo group (P-value for all>0.05). There was no significant interaction between sex and treatment-related discontinuation for hypotension (P=0.520), an increase in creatinine (P=0.102), and hyperkalaemia (P=0.905). In a randomized clinical trial in patients with HFrEF, men and women achieved similar doses of candesartan. Primary event rates and treatment-related discontinuation due to adverse events were also similar between men and women.

Clinical significance of R-wave amplitude in lead V1 and inferobasal myocardial infarction in patients with inferior wall myocardial infarction.

To assess electrocardiogram (ECG) for risk stratification in inferior ST-elevation myocardial infarction (STEMI) patients within 24 h. Three hundred thirty-four patients were divided into four ECG-based groups: Group A: R V1 <0.3 mV with ST-segment elevation (ST↑) V7-V9, Group B: R V1 <0.3 mV without ST↑ V7-V9, Group C: R V1 ≥0.3 mV with ST↑ V7-V9, and Group D: R V1 ≥0.3 mV without ST↑ V7-V9. Group A demonstrated the longest QRS duration, followed by Groups B, C, and D. ECG signs for right ventricle (RV) infarction were more common in Groups A and B (p < .01). ST elevation in V6, indicative of left ventricle (LV) lateral injury, was more higher in Group C than in Group A, while the ∑ST↑ V3R + V4R + V5R, representing RV infarction, showed the opposite trend (p < .05). The estimated LV infarct size from ECG was similar between Groups A and C, yet Group A had higher creatine kinase MB isoform (CK-MB; p < .05). Cardiac troponin I (cTNI) was higher in Groups A and C than in B and D (p < .05 and p = .16, respectively). NT-proBNP decreased across groups (p = .20), with the highest left ventricular ejection fraction (LVEF) observed in Group D (p < .05). Group A notably demonstrated more cardiac dysfunction within 4 h post-onset. For inferior STEMI patients, concurrent R V1 <0.3 mV with ST↑ V7-V9 suggests prolonged ventricular activation and notable myocardial damage. RV infarction's dominance over LV lateral injury might explain these observations.

Sequential Treatment of Acute Heart Failure in the Elderly: Efficacy of Recombinant Human Brain Natriuretic Peptide and Sacubitril-Valsartan

Objective: To explore the clinical efficacy of recombinant human brain natriuretic peptide (rhBNP) and sacubitril-valsartan in the sequential treatment of acute heart failure (AHF) in older individuals. Methods: Clinical data from 64 older patients with AHF were collected for this study. The patients were divided into two groups: a control group (Group A, n = 34) and an observation group (Group B, n = 30) based on different treatment regimens. Group A received rhBNP treatment, while Group B received sequential treatment with rhBNP and Sacubitril-Valsartan. The evaluation of the sequential treatment’s effect on older patients with AHF was conducted using various indicators. Results: The clinical efficacy rate in Group A (93.33%) was significantly higher than that in Group A (73.53%), with a significant difference observed (P &lt; 0.05). Furthermore, after treatment, the clinical efficacy remained significantly higher in Group B than in Group A. Group B exhibited a significantly higher left ventricular ejection fraction (LVEF) and significantly lower systolic blood pressure, diastolic blood pressure, and heart rate compared to Group A (P &lt; 0.05). Although the left ventricular end-diastolic diameter (LVEDD) was lower in Group B after treatment, the difference was not statistically significant (P = 0.127). Moreover, post-treatment levels of NT-proBNP were significantly lower in Group B compared to Group A (P = 0.01). Additionally, Group B had shorter hospitalization times, faster improvement in clinical symptoms, and further 6-minute walking distances after the treatment compared to Group A (P &lt; 0.01). Conclusion: Sequential treatment with rhBNP and Sacubitril-Valsartan demonstrates promising therapeutic effects in older patients with AHF, suggesting its potential for broader adoption and promotion in clinical practice.

The Effect of Percutaneous Coronary Intervention in Elderly Patients with Coronary Heart Disease and Its Impact on Cardiac Function Indicators

Objective: To analyze the role of percutaneous coronary intervention and its value in elderly patients with coronary heart disease. Methods: A total of 88 elderly patients diagnosed with coronary heart disease between June 2022 and June 2023 were recruited and divided into two groups using the random number table method, with 44 cases in each group. The control group received conventional drug therapy, while the observation group received percutaneous arterial interventional treatment in addition to conventional drug therapy. Clinical efficacy, adverse cardiovascular events, cardiac function indicators, and quality of life were observed in both groups. Results: The observation group demonstrated a significantly higher total effective rate and significantly lower adverse cardiovascular events (P &lt; 0.05). Furthermore, after treatment, the observation group showed a higher left ventricular ejection fraction, as well as lower left ventricular end-systolic diameter, left ventricular end-systolic volume, left ventricular end-diastolic diameter, and left ventricular end-diastolic volume (P &lt; 0.05). Additionally, the observation group had higher scores in all eight dimensions of the SF-36 scale (P &lt; 0.05). Conclusion: For elderly patients diagnosed with coronary heart disease, percutaneous coronary intervention can achieve superior clinical efficacy and high safety and can help improve cardiac function indicators and quality of life.

Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial.

Heart failure triggers a shift in myocardial metabolic substrate utilization, favoring the ketone body 3-hydroxybutyrate as energy source. We hypothesized that 14-day treatment with ketone ester (KE) would improve resting and exercise hemodynamics and exercise capacity in patients with heart failure with reduced ejection fraction. In a randomized, double-blind cross-over study, nondiabetic patients with heart failure with reduced ejection fraction received 14-day KE and 14-day isocaloric non-KE comparator regimens of 4 daily doses separated by a 14-day washout period. After each treatment period, participants underwent right heart catheterization, echocardiography, and blood sampling at plasma trough levels and after dosing. Participants underwent an exercise hemodynamic assessment after a second dosing. The primary end point was resting cardiac output (CO). Secondary end points included resting and exercise pulmonary capillary wedge pressure and peak exercise CO and metabolic equivalents. We included 24 patients with heart failure with reduced ejection fraction (17 men; 65±9 years of age; all White). Resting CO at trough levels was higher after KE compared with isocaloric comparator (5.2±1.1 L/min versus 5.0±1.1 L/min; difference, 0.3 L/min [95% CI, 0.1-0.5), and pulmonary capillary wedge pressure was lower (8±3 mm Hg versus 11±3 mm Hg; difference, -2 mm Hg [95% CI, -4 to -1]). These changes were amplified after KE dosing. Across all exercise intensities, KE treatment was associated with lower mean exercise pulmonary capillary wedge pressure (-3 mm Hg [95% CI, -5 to -1] ) and higher mean CO (0.5 L/min [95% CI, 0.1-0.8]), significantly different at low to moderate steady-state exercise but not at peak. Metabolic equivalents remained similar between treatments. In exploratory analyses, KE treatment was associated with 18% lower NT-proBNP (N-terminal pro-B-type natriuretic peptide; difference, -98 ng/L [95% CI, -185 to -23]), higher left ventricular ejection fraction (37±5 versus 34±5%; P=0.01), and lower left atrial and ventricular volumes. KE treatment for 14 days was associated with higher CO at rest and lower filling pressures, cardiac volumes, and NT-proBNP levels compared with isocaloric comparator. These changes persisted during exercise and were achieved on top of optimal medical therapy. Sustained modulation of circulating ketone bodies is a potential treatment principle in patients with heart failure with reduced ejection fraction. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05161650.

Sacubitril/Valsartan-Related Hypotension in Patients With Heart Failure and Preserved or Mildly Reduced Ejection Fraction

BackgroundHypotension is a potential adverse effect of sacubitril/valsartan, but there are limited data regarding the predictors and implications of treatment-related hypotension in heart failure (HF) with mildly reduced and preserved ejection fraction. ObjectivesWe investigated predictors of treatment-associated hypotension, clinical outcomes after hypotension, and the relationship between left ventricular ejection fraction (LVEF) and incidence of hypotension in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) trial. MethodsPARAGON-HF randomized patients with chronic HF (≥45%) to sacubitril/valsartan or valsartan. Following randomization, hypotension was defined as investigator-reported hypotension with a systolic blood pressure <100 mm Hg. Predictors of hypotension were assessed using multivariable Cox models. Associations between hypotension and clinical outcomes were evaluated in time-updated Cox models. The relationship among treatment, LVEF, and incident rates of hypotension and clinical outcomes was estimated using Poisson regression models. ResultsOf 4,796 patients in PARAGON-HF, 637 (13%) experienced hypotension, more frequently in the sacubitril/valsartan arm (P < 0.001). Following documented hypotension, patients had higher risk of cardiovascular death and total HF hospitalizations (adjusted RR: 1.63; 95% CI: 1.27-2.09; P < 0.001) and all-cause death (adjusted HR: 1.62; 95% CI: 1.28-2.05; P < 0.001). LVEF modified the association between sacubitril/valsartan and risk of hypotension (Pinteraction = 0.019) such that patients with LVEF ≥60% experienced substantially higher treatment-related risks of hypotension. ConclusionsIn PARAGON-HF, a higher LVEF was associated with an increased risk of hypotension in patients treated with sacubitril/valsartan compared with valsartan. Because these subjects are also less likely to derive clinical benefit from sacubitril/valsartan, our data reinforce that the benefit/risk ratio favors the use of sacubitril/valsartan in patients with LVEF below normal, but not at higher LVEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)

Impact of heart rate changes during hospitalization on outcome in heart failure with preserved ejection fraction.

The benefits of lowering heart rate (HR) in heart failure (HF) with preserved ejection fraction (HFpEF) patients are still a matter of debate. This study aimed to investigate the relationship between changes in HR during hospitalization and cardiovascular (CV) events and all-cause death in hospitalized HFpEF patients. Hospitalized HF patients between January 2017 and December 2021 were consecutively enrolled in a national, multicentred, and prospective registry database, the China Cardiovascular Association Database-HF Center Registry. HF patients with a left ventricular ejection fraction of ≥50% were defined as HFpEF patients. The study analysed admission/discharge HR, change in HR during hospitalization (∆HR), and ∆HR ratio (∆HR/admission HR). The patients were categorized into three groups: no HR dropping group (ΔHR ratio>0.0%), moderate HR dropping group (-15%<ΔHR ratio≤0.0%), and excessive HR dropping group (ΔHR ratio≤-15%). All patients were followed up for 12months. The primary endpoint was CV events (CV death or HF rehospitalization). The secondary endpoint was all-cause death. A total of 19510 HFpEF patients (9750 males, mean age 71.9±12.2years) were included, with 4575 in the no HR dropping group, 8434 in the moderate HR dropping group, and 6501 in the excessive HR dropping group. Excessive HR dropping during hospitalization was significantly associated with an increased risk of CV events (17.1%) compared with the no HR dropping group (14.5%, P<0.001) or the moderate HR dropping group (14.0%, P<0.001), although all-cause mortality was similar among the three groups. After adjusting for multiple confounding factors, excessive HR dropping remained an independent predictor of increased CV event risk [hazard ratio 1.197, 95% confidence interval (CI) 1.078-1.328]. Subgroup analysis revealed that the prognostic impact of excessive HR dropping on increased CV event risk remained in the subgroups of older age, New York Heart Association class IV, ischaemic HF, higher left ventricular ejection fraction, absence of chronic kidney disease, and use of beta-blockers or ivabradine. Independent determinants associated with excessive HR dropping during admission included use of beta-blockers [odds ratio (OR) 1.683, 95% CI 1.558-1.819], lower discharge diastolic blood pressure (OR 0.988, 95% CI 0.985-0.991), no pacemaker (OR 0.501, 95% CI 0.416-0.603), coexisting atrial fibrillation or atrial flutter (OR 1.327, 95% CI 1.218-1.445), and use of digoxin (OR 1.340, 95% CI 1.213-1.480). In hospitalized HFpEF patients, excessive HR dropping during hospitalization is associated with an increased risk of CV death or HF rehospitalization. These findings highlight the importance of HR monitoring and avoiding excessively slowing down HR in hospitalized HFpEF patients to reduce the risk of CV events.

Recombinant human soluble domain of CD39L3 and ticagrelor: cardioprotective effects in experimental myocardial infarction.

The ecto-nucleoside triphosphate diphosphohydrolases of the CD39 family degrade ATP and ADP into AMP, which is converted into adenosine by the extracellular CD73/ecto-5-nucleotidase. This pathway has been explored in antithrombotic treatments but little in myocardial protection. We have investigated whether the administration of solCD39L3 (AZD3366) confers additional cardioprotection to that of ticagrelor alone in a pre-clinical model of myocardial infarction (MI). Ticagrelor-treated pigs underwent balloon-induced MI (90 min) and, before reperfusion, received intravenously either vehicle, 1 mg/kg AZD3366 or 3 mg/kg AZD3366. All animals received ticagrelor twice daily for 42 days. A non-treated MI group was run as a control. Serial cardiac magnetic resonance (baseline, Day 3 and Day 42 post-MI), light transmittance aggregometry, bleeding time, and histological and molecular analyses were performed. Ticagrelor reduced oedema formation and infarct size at Day 3 post-MI vs. controls. A 3 mg/kg AZD3366 provided an additional 45% reduction in oedema and infarct size compared with ticagrelor and a 70% reduction vs. controls (P < .05). At Day 42, infarct size declined in all ticagrelor-administered pigs, particularly in 3 mg/kg AZD3366-treated pigs (P < .05). Left ventricular ejection fraction was diminished at Day 3 in placebo pigs and worsened at Day 42, whereas it remained unaltered in ticagrelor ± AZD3366-administered animals. Pigs administered with 3 mg/kg AZD3366 displayed higher left ventricular ejection fraction upon dobutamine stress at Day 3 and minimal dysfunctional segmental contraction at Day 42 (χ2P < .05 vs. all). Cardiac and systemic molecular readouts supported these benefits. Interestingly, AZD3366 abolished ADP-induced light transmittance aggregometry without affecting bleeding time. Infusion of AZD3366 on top of ticagrelor leads to enhanced cardioprotection compared with ticagrelor alone.

The severity of chronic heart failure and the parameters of daily blood pressure profile in patients with coronary heart disease

Aim: Although the prevalence of coronary heart disease (CHD) and hypertension which are the most common causes of the development and progression of chronic heart failure (CHF) is high, 24-hour ambulatory blood pressure (BP) monitoring (ABPM) in patients with CHF is not mandatory to be performed. The growing number of evidence suggests that excessive decrease in BP which clearly reflects increased BP variability (BPV) affects the survival of patients with heart failure (HF). The objective of the study was to investigate the relationship between the parameters specific to CHF severity and features of daily BP profiles in patients with ischemic CHF and hypertension. Methods: Ninety patients with functional class II–IV of CHF and CHD (the main group) and 50 non-CHF patients with hypertension (the comparative group) were examined. The transthoracic echocardiography (TTE) [atrial end-systolic dimension (ESD), ventricular end-diastolic dimension (EDD), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF)] and 24-hour ABPM (BPV parameters and proportions of hypotensive episodes) were performed. The relationships between the abovementioned parameters were evaluated using the univariate correlation analysis and stepwise multiple linear regression. Results: Higher functional class of CHF is found to be associated with a higher incidence of daytime systolic BP (SBP) decline and nighttime SBP and diastolic BP (DBP) variability while higher LVEF is related to the hypotensive episodes regardless of CHF. Conclusions: It appears that the larger trials involving CHF patients with reduced LVEF should be conducted to clarify the obtained results.

CMR Predictors of Favorable Outcome in Myocarditis: A Single-Center Experience.

Background: Cardiovascular magnetic resonance (CMR) has emerged as the most accurate, non-invasive method to support the diagnosis of clinically suspected myocarditis and as a risk-stratification tool in patients with cardiomyopathies. We aim to assess the diagnostic and prognostic role of CMR at diagnosis in patients with myocarditis. Methods: We enrolled consecutive single-center patients with 2013 ESC consensus-based endomyocardial biopsy (EMB)-proven or clinically suspected myocarditis undergoing CMR at diagnosis. The pre-specified outcome was defined as NYHA class > I and echocardiographic left ventricular ejection fraction (LVEF) < 50% at follow-up. Results: We included 207 patients (74% male, median age 36 years; 25% EMB-proven). CMR showed the highest sensitivity in myocarditis with infarct-like presentation. Patients with EMB-proven myocarditis were more likely to have diffuse LGE and right ventricular LGE (p < 0.001), which was also more common among patients with arrhythmic presentation (p = 0.001). The outcome was met in 17 patients at any follow-up time point, more commonly in those with larger biventricular volumes (p < 0.001), CMR-based diagnosis of dilated cardiomyopathy (p < 0.001), and ischemic LGE (p = 0.005). Higher biventricular systolic function (p < 0.001) and greater LGE extent (p = 0.033) at diagnosis had a protective effect. Conclusions: In our single-center cohort of rigorously defined myocarditis patients, higher biventricular systolic function and greater LGE extent on CMR at diagnosis identified patients with better functional class and higher left ventricular ejection fraction at follow-up. Conversely, larger biventricular volumes, CMR-based DCM features, and the presence of an ischemic LGE pattern at diagnosis were predictors of worse functional class and LV systolic dysfunction at follow-up. Larger prospective studies are warranted to extend our findings to multi-center cohorts.

Comparison of clinical efficacy and prognosis between interventional occlusion and surgical treatment for acute myocardial infarction with ventricular septal perforation.

This retrospective study compared the clinical outcomes and prognostic factors in acute myocardial infarction-related patients with inter-ventricular septal perforation (AMI-VSP) who underwent interventional occlu-sion (IO group) or surgical intervention (SI group). Forty-six patients were ana-lyzed based on comprehensive clinical data, laboratory results, and follow-up evaluations. The SI group had higher EuroScore II scores and more patients in Killip class IV. Both treatments showed improved laboratory indices, but the IO group had higher left ventricular ejection fraction and lower levels of specific biomarkers. The postoperative hospital stay and total hospitalization time were shorter in the IO group. Survival rates did not significantly differ between the two groups during the follow-up period. Logistic regression analysis identified a history of coronary heart disease as a significant risk factor affecting progno-sis and survival rates. Both interventional occlusion and surgical intervention proved effective, with IO showing faster recovery and more favorable prognoses, while surgery was preferred for severe cases. Coronary heart disease was a key factor influencing postoperative survival in AMI-VSP patients.