Higher Ejection Fraction Research Articles

Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion.

Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). Reperfusion injury hampers myocardial recovery in a clinical setting and its management is an unmet need. We investigated the efficacy of intracoronary (IC) delivery of xenogeneic hUCM-MSC as reperfusion-adjuvant therapy in a translational model of AMI in swine. In a placebo-controlled trial, pot-belied pigs were randomly assigned to a sham-control group (vehicle-injection; n = 8), AMI + vehicle (n = 12) or AMI + IC-injection (n = 11) of 5 × 105 hUCM-MSC/Kg, within 30 min of reperfusion. AMI was created percutaneously by balloon occlusion of the mid-LAD. Left-ventricular function was blindly evaluated at 8-weeks by invasive pressure-volume loop analysis (primary endpoint). Mechanistic readouts included histology, strength-length relationship in skinned cardiomyocytes and gene expression analysis by RNA-sequencing. As compared to vehicle, hUCM-MSC enhanced systolic function as shown by higher ejection fraction (65 ± 6% vs. 43 ± 4%; p = 0.0048), cardiac index (4.1 ± 0.4 vs. 3.1 ± 0.2 L/min/m2; p = 0.0378), preload recruitable stroke work (75 ± 13 vs. 36 ± 4 mmHg; p = 0.0256) and end-systolic elastance (2.8 ± 0.7 vs. 2.1 ± 0.4 mmHg*m2/ml; p = 0.0663). Infarct size was non-significantly lower in cell-treated animals (13.7 ± 2.2% vs. 15.9 ± 2.7%; Δ = -2.2%; p = 0.23), as was interstitial fibrosis and cardiomyocyte hypertrophy in the remote myocardium. Sarcomere active tension improved, and genes related to extracellular matrix remodelling (including MMP9, TIMP1 and PAI1), collagen fibril organization and glycosaminoglycan biosynthesis were downregulated in animals treated with hUCM-MSC. Intracoronary transfer of xenogeneic hUCM-MSC shortly after reperfusion improved left-ventricular systolic function, which could not be explained by the observed extent of infarct size reduction alone. Combined contributions of favourable modification of myocardial interstitial fibrosis, matrix remodelling and enhanced cardiomyocyte contractility in the remote myocardium may provide mechanistic insight for the biological effect.

Arrhythmogenicity of anti-tachycardia pacing in patients with implantable cardioverter defibrillator

BackgroundAnti-tachycardia pacing therapy (ATP) has shown comparable efficacy to shock therapy in ventricular tachycardia (VT) termination with better quality of life. However, some ATPs may lead to VT acceleration or degeneration to ventricular fibrillation (VF), which will result in more ICD shocks. The aim of this study was to investigate the predictors of VT acceleration by ATP therapy in a real-life patient cohort.ResultsWe retrospectively reviewed 448 monomorphic VT episodes that required ATP therapy in 60 patients with structural heart diseases implanted with ICD or CRTD. The clinical data of the patients and the episodes’ details were evaluated. We found that patients with a higher ejection fraction (EF) were more likely to be cardioverted by ATP therapy (P: 0.024). VT acceleration was more frequent in patients with lower EF (mean 31.24 ± 4.08) compared with the non-accelerated patients with higher EF (mean 37.00 ± 9.4, P: 0.016). The percentage of accelerated episodes was 8.5%. VT episodes with a mean cycle length (CL) < 310 ms are more likely to accelerate (sensitivity 76.3%, specificity 67.7%, PPV value 45%, NPV 86%, and AUC 0.790). There was a statistically significant difference in the accelerated VT episodes as compared to non-accelerated episodes regarding the number of ATP bursts (mean 3.66 ± 2.22 vs. 1.76 ± 1.35, P: < 0.001), ramp (23.7% vs. 4.2%, P: < 0.001), scanning (55.3% vs. 31.3%, P: 0.003) and burst adaptive cycle length (mean 83.55 ± 2.92 vs. 84.64 ± 2.61, P: 0.016). In a multivariate analysis, the VT CL, number of ATP bursts and ramp pacing predicted VT acceleration by ATP therapy.ConclusionsVentricular tachycardia in patients with low LV EF and fast VTs with a CL less than 310 ms were more likely to accelerate with ATP therapy. The number of ATP bursts and the use of ramp had a significant effect on VT acceleration. To avoid VT acceleration by ATP therapy, ramp pacing better be avoided, especially in fast VTs, and lesser number of bursts should be delivered.

Discrepancy between invasive and echocardiographic transvalvular gradient after TAVI: Insights from the LAPLACE-TAVI registry

BackgroundEchocardiography-based transvalvular mean pressure gradient (ECHO-mPG) used to assess the forward valve function and structural valve deterioration could overestimate the true pressure gradient. This study evaluated the discrepancy between invasive and ECHO-mPG after transcatheter aortic valve implantation (TAVI) with respective valve type and size, its impact on a device success criterion, and predictors of a pressure discrepancy. MethodsWe analyzed 645 patients registered in a multicenter TAVI registry (balloon-expandable valve [BEV]: 500; self-expandable valve [SEV]: 145). The invasive transvalvular mPG was measured after valve implantation using two Pigtail catheters (CATH-mPG), while the ECHO-mPG was measured within 48 h after TAVI. Pressure recovery (PR) was calculated using the following formula: ECHO-mPG × effective orifice area (EOA)/ascending aortic area (AoA) × (1 − EOA/AoA). ResultsECHO-mPG was weakly correlated with (r = 0.29, p < 0.0001), and consistently overestimated CATH-mPG in both BEV and SEV, and respective valve sizes. The magnitude of the discrepancy was larger for BEV than SEV (p < 0.001) and smaller valves (p < 0.001). After the correction of PR using the above formula, the pressure discrepancy remained for BEV (p < 0.001) but not SEV (p = 0.10). The proportion of patients with an ECHO-mPG > 20 mmHg decreased from 7.0% to 1.6% after correction (p < 0.0001). Among the baseline and procedural variables, post-procedural ejection fraction, BEV versus SEV, and smaller valves were associated with a larger discrepancy in mPG. ConclusionsECHO-mPG could be overestimated after TAVI, especially in patients with a smaller BEV. A higher ejection fraction, BEV, and smaller valves were predictors of a pressure discrepancy between CATH- and ECHO-mPG.

Beta-Blocker Use and Heart Failure Outcomes in Mildly Reduced and Preserved Ejection Fraction

BackgroundAlthough studies consistently show that beta-blockers reduce morbidity and mortality in patients with reduced ejection fraction (EF), data are inconsistent in patients with heart failure with mildly reduced ejection fraction (HFmrEF) and suggest potential negative effects in heart failure with preserved ejection fraction (HFpEF). ObjectivesThe purpose of this study was to examine the association of beta-blockers with heart failure (HF) hospitalization and death in patients with HF and EF ≥40% MethodsBeta-blocker use was assessed at first encounter in outpatients ≥65 years of age with HFmrEF and HFpEF in the U.S. PINNACLE Registry (2013-2017). The associations of beta-blockers with HF hospitalization, death, and the composite of HF hospitalization/death were assessed using propensity-score adjusted multivariable Cox regression models, including interactions of EF × beta-blocker use. ResultsAmong 435,897 patients with HF and EF ≥40% (HFmrEF, n = 75,674; HFpEF = 360,223), 289,377 (66.4%) were using a beta-blocker at first encounter; more commonly in patients with HFmrEF vs HFpEF (77.7% vs 64.0%; P < 0.001). There were significant interactions between EF × beta-blocker use for HF hospitalization, death, and composite of HF hospitalization/death (P < 0.001 for all), with higher risk with beta-blocker use as EF increased. Beta-blockers were associated with decreased risk of HF hospitalization and death in patients with HFmrEF but a lack of survival benefit and a higher risk of HF hospitalization in patients with HFpEF, particularly when EF was >60%. ConclusionsIn a large, real-world, propensity score-adjusted cohort of older outpatients with HF and EF ≥40%, beta-blocker use was associated with a higher risk of HF hospitalization as EF increased, with potential benefit in patients with HFmrEF and potential risk in patients with higher EF (particularly >60%). Further studies are needed to understand the appropriateness of beta-blocker use in patients with HFpEF in the absence of compelling indications.

Assessment of Diastolic Function of Heart Failure Patients Due to Systemic Hypertension

Introduction: Diastolic function as is the current conventional tradition, in order to gain deeper understanding it is more useful to view diastolic function as a problem to be solved! Once the basic problem of normal physiology of diastole has been mastered, it is nearly self-evident as to what the issues are in clinical heart failure and which physiologic mechanism and its hard-wired compensatory pathways one is confronted with. Objective: To evaluate diastolic function of heart failure patients with systemic hypertension. Methods: The present prospective observational study was undertaken in Cardiology Department, Dhaka Medical College hospital, Dhaka, Bangladesh from January to July, 2019. Fifty-four (54) patients with systemic hypertension who recently experienced heart failure with normal ejection fraction (≥50%) and no clinical history of ischaemic cardiomyopathy were studied. The patients were divided into two groups according to the degree of echocardiographic hypertrophy: Group-I (28 patients) with a ventricular mass/volume ratio &gt;1.8 and group-II (26 patients) with a ratio &lt;1.8. Results: Total 54 patients with diastolic dysfunction with hypertension were included in the study. Shows the age and sex distribution with highest frequency in the age group 61-70 years, comprising 31.5 percent and 51-60 years 25.9 percent, 41-50 year 24.1 percent, 71 + years 12.9 percent and 30-40 years 5.6 percent in descending order. Group I patients had a higher ejection fraction (67.62±3.14 vs 55.33 ±4.13, P&lt;0.001), smaller ventricular diameter (28.88±2.46 vs 34.38±4.37, P&lt;0.001), higher LV mass (154.42±6.80 vs 123.38±5.58, P&lt;0.001), lower ETT positivity (14%vs73%, P&lt;0.001). Clinically, group I had more frequent audible fourth heart sound (57% vs 21%, P&lt; 0.001), low incidence of audible third heart sound (17% vs 69%, P&lt;0.001), ECG evident LVH (96% vs 15%, P&lt;0.001), cardiomegaly (25% vs 73%, P&lt;0.001). Conclusion: There were no significant differences between groups ..........

Cardiac MRI: An Alternative Method to Determine the Left Ventricular Function.

(1) Background: With the conventional contour surface method (KfM) for the evaluation of cardiac function parameters, the papillary muscle is considered to be part of the left ventricular volume. This systematic error can be avoided with a relatively easy-to-implement pixel-based evaluation method (PbM). The objective of this thesis is to compare the KfM and the PbM with regard to their difference due to papillary muscle volume exclusion. (2) Material and Methods: In the retrospective study, 191 cardiac-MR image data sets (126 male, 65 female; median age 51 years; age distribution 20-75 years) were analysed. The left ventricular function parameters: end-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (EF) and stroke volume (SV) were determined using classical KfW (syngo.via and cvi42 = gold standard) and PbM. Papillary muscle volume was calculated and segmented automatically via cvi42. The time required for evaluation with the PbM was collected. (3) Results: The size of EDV was 177 mL (69-444.5 mL) [average, [minimum-maximum]], ESV was 87 mL (20-361.4 mL), SV was 88 mL and EF was 50% (13-80%) in the pixel-based evaluation. The corresponding values with cvi42 were EDV 193 mL (89-476 mL), ESV 101 mL (34-411 mL), SV 90 mL and EF 45% (12-73%) and syngo.via: EDV 188 mL (74-447 mL), ESV 99 mL (29-358 mL), SV 89 mL (27-176 mL) and EF 47% (13-84%). The comparison between the PbM and KfM showed a negative difference for end-diastolic volume, a negative difference for end-systolic volume and a positive difference for ejection fraction. No difference was seen in stroke volume. The mean papillary muscle volume was calculated to be 14.2 mL. The evaluation with PbM took an average of 2:02 min. (4) Conclusion: PbM is easy and fast to perform for the determination of left ventricular cardiac function. It provides comparable results to the established disc/contour area method in terms of stroke volume and measures "true" left ventricular cardiac function while omitting the papillary muscles. This results in an average 6% higher ejection fraction, which can have a significant influence on therapy decisions.

Ventricular stiffening and chamber contracture in heart failure with higher ejection fraction.

Ancillary analyses from clinical trials have suggested reduced efficacy for neurohormonal antagonists among patients with heart failure and preserved ejection fraction (HFpEF) and higher ranges of ejection fraction (EF). A total of 621 patients with HFpEF were grouped into those with low-normal left ventricular EF (LVEF) (HFpEF<65% , n = 319, 50% ≤ LVEF <65%) or HFpEF≥65% (n = 302, LVEF ≥65%), and compared with 149 age-matched controls undergoing comprehensive echocardiography and invasive cardiopulmonary exercise testing. A sensitivity analysis was performed in a second non-invasive community-based cohort of patients with HFpEF (n = 244) and healthy controls without cardiovascular disease (n = 617). Patients with HFpEF≥65% had smaller left ventricular (LV) end-diastolic volume than HFpEF<65% , but LV systolic function assessed by preload recruitable stroke work and stroke work/end-diastolic volume was similarly impaired. Patients with HFpEF≥65% displayed an end-diastolic pressure-volume relationship (EDPVR) that was shifted leftward, with increased LV diastolic stiffness constant β, in both invasive and community-based cohorts. Cardiac filling pressures and pulmonary artery pressures at rest and during exercise were similarly abnormal in all EF subgroups. While patients HFpEF≥57% displayed leftward shifted EDPVR, those with HFpEF<57% had a rightward shifted EDPVR more typical of heart failure with reduced EF. Most pathophysiologic differences in patients with HFpEF and higher EF are related to smaller heart size, increased LV diastolic stiffness, and leftward shift in the EDPVR. These findings may help to explain the absence of efficacy for neurohormonal antagonists in this group and raise a new hypothesis, that interventions to stimulate eccentric LV remodelling and enhance diastolic capacitance may be beneficial for patients with HFpEF and EF in the higher range.

Disparities in prevalence of heart failure between the genders in relation to age, multimorbidity and socioeconomic status in southern Sweden: a cross-sectional study

Objective Prior studies have reported that heart failure typically affects elderly, multimorbid and socioeconomically deprived men. Women with heart failure are generally older, have a higher EF (ejection fraction) and have more heart failure-related symptoms than men. This study explored the disparities in the prevalence of heart failure between men and women in relation to age, multimorbidity level and socioeconomic status of the population in southern Sweden. Design A register-based, cross-sectional cohort study. Setting and subjects: The inhabitants from 20 years of age onwards (N = 981,383) living in southern Sweden in 2015. Main outcome measure: Prevalence and mean probability of having heart failure in both genders. CNI (Care Need Index) percentiles depend on the socioeconomic status of their listed primary healthcare centres. Results Men had a higher OR for HF − 1.70 (95% CI 1.65–1.75) - than women. The probability of men having heart failure increased significantly compared to women with advancing age and multimorbidity levels. At all CNI levels, the multimorbid patients had a higher prevalence of heart failure in men than in women. The disparity in the mean probability of heart failure between the most affluent and deprived CNI percentile was more apparent in women compared to men, especially from 80 years. Conclusions The prevalence of heart failure differs significantly between the genders. Men had an increasing mean probability of heart failure with advancing age and multimorbidity level compared to women. Socioeconomic deprivation was more strongly associated with heart failure in women than in men. The probability of having heart failure differs between the genders in several aspects. Key Points Independently of socioeconomic status, men had a higher prevalence of heart failure than women among the multimorbid patients. The mean probability of men having heart failure increased significantly compared to women with advancing age and multimorbidity level. Socioeconomic status was more strongly associated with heart failure in women than in men.

Apical Ischemia Is a Universal Feature of Apical Hypertrophic Cardiomyopathy.

Apical hypertrophic cardiomyopathy (ApHCM) accounts for ≈10% of hypertrophic cardiomyopathy cases and is characterized by apical hypertrophy, apical cavity obliteration, and tall ECG R waves with ischemic-looking deep T-wave inversion. These may be present even with <15 mm apical hypertrophy (relative ApHCM). Microvascular dysfunction is well described in hypertrophic cardiomyopathy. We hypothesized that apical perfusion defects would be common in ApHCM. A 2-center study using cardiovascular magnetic resonance short- and long-axis quantitative adenosine vasodilator stress perfusion mapping. One hundred patients with ApHCM (68 overt hypertrophy [≥15 mm] and 32 relative ApHCM) were compared with 50 patients with asymmetrical septal hypertrophy hypertrophic cardiomyopathy and 40 healthy volunteer controls. Perfusion was assessed visually and quantitatively as myocardial blood flow and myocardial perfusion reserve. Apical perfusion defects were present in all overt ApHCM patients (100%), all relative ApHCM patients (100%), 36% of asymmetrical septal hypertrophy hypertrophic cardiomyopathy, and 0% of healthy volunteers (P<0.001). In 10% of patients with ApHCM, perfusion defects were sufficiently apical that conventional short-axis views missed them. In 29%, stress myocardial blood flow fell below rest values. Stress myocardial blood flow was most impaired subendocardially, with greater hypertrophy or scar, and with apical aneurysms. Impaired apical myocardial blood flow was most strongly predicted by thicker apical segments (β-coefficient, -0.031 mL/g per min [CI, -0.06 to -0.01]; P=0.013), higher ejection fraction (-0.025 mL/g per min [CI, -0.04 to -0.01]; P<0.005), and ECG maximum R-wave height (-0.023 mL/g per min [CI, -0.04 to -0.01]; P<0.005). Apical perfusion defects are universally present in ApHCM at all stages. Its ubiquitous presence along with characteristic ECG suggests ischemia may play a disease-defining role in ApHCM.

Myocardial angiogenesis induced by concurrent vitamin D supplementation and aerobic-resistance training is mediated by inhibiting miRNA-15a, and miRNA-146a and upregulating VEGF/PI3K/eNOS signaling pathway.

This study aimed to investigate the effects of co-treatment of aerobic-resistance training (ART), vitamin D3 (VD3) on cardiovascular function considering the involvement of microRNA-15a and microRNA-146a, vascular endothelial growth factor (VEGF), phosphatidylinositol-3 kinase (PI3K), and endothelial nitric oxide synthase (eNOS) after myocardial infarction (MI) in rats. To induce MI, male Wistar rats subcutaneously received isoproterenol for 2 days, then MI was confirmed by echocardiography. MI rats were divided into six groups (n = 8/group). MI + VD3, MI + sesame oil (Veh), MI + ART, MI + VD3 + ART, and MI + Veh + ART, and received the related treatments for 8 weeks. Exercise tests, echocardiography, real-time quantitative polymerase chain reaction (qRT-PCR), western blotting, and histological staining were performed after the end of treatments. The highest ejection fraction (EF%), fractional shortening (FS%), exercise capacity (EC), and maximal load test (MLT) amounts were observed in the groups treated with VD3, ART, and VD3 + ART (P < 0.05). These were accompanied by a significantly increased angiogenesis post-MI. Furthermore, the levels of circulating microRNA-15a and microRNA-146a were significantly decreased in these groups compared to MI rats that were together with a significant upregulation of cardiac VEGF, PI3K, and eNOS expression. Overall, the best results were observed in the group treated with VD3 + ART. Concurrent VD3 supplementation and ART attenuated microRNA-15a and microRNA-146a and induced angiogenesis via VEGF/PI3K/eNOS axis. This data demonstrate that concurrent VD3 supplementation and ART is a more efficient strategy than monotherapy to improve cardiac function post-MI.

The Relationship Between PRECISE-DAPT Score and Spontaneous Reperfusion of Infarct-Related Artery in Patients with ST-Segment Elevation Myocardial Infarction.

Spontaneous reperfusion (SR) presence and a low PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti Platelet Therapy (PRECISE-DAPT) score in patients with acute coronary syndrome have been associated with favorable clinical outcomes. This study aimed to investigate the relationship between SR and this score. The study included 436 patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). Thrombolysis in myocardial infarction (TIMI) III blood flow presence in the infarct-related artery (IRA) before primary percutaneous coronary intervention (PCI) was defined as SR. Patients were categorized into two groups based on the presence (n = 49) or absence (n = 387) of SR. The PRECISE-DAPT score was computed for each patient using the web-based calculator. The group with SR had a lower frequency of hyperlipidemia and a higher ejection fraction (EF) at admission. Conversely, the group without SR presented with higher values of glucose, troponin, creatine kinase-myocardial band (CK-MB), and PRECISE-DAPT score. The no-reflow phenomenon and elevated SYNergy between PCI with TAXUS and Cardiac Surgery (SYNTAX-I) scores were higher in the group without SR than in the one with SR. Multivariate regression analysis indicated that a high PRECISE-DAPT score was an independent predictor of the absence of SR (odds ratio: 0.96, P = 0.04). The PRECISE-DAPT score is an independent predictor of the presence of spontaneous reperfusion in patients who experienced STEMI.

Prognostic value of age, creatinine, and left ventricular ejection fraction risk score in patients evaluated with fractional flow reserve: a cross-sectional study.

In this study, we investigated the relationship between age, creatinine, and left ventricular ejection fraction risk score and the severity of coronary lesions detected by applying fractional flow reserve in the patient group presenting with chronic coronary syndrome. Also, we presented long-term follow-up results in patients whose age, creatinine, and left ventricular ejection fraction score was evaluated by the fractional flow reserve procedure. This study was planned retrospectively and in two centers. For this purpose, 114 patients who met the study criteria and who underwent elective fractional flow reserve between January 2014 and January 2019 were included in the study. Age, creatinine, and left ventricular ejection fraction was calculated as age/left ventricular ejection fraction +1 (if estimated glomerular filtration rate<30 mL/min). They were divided into two groups according to the cutoff value of the age, creatinine, and left ventricular ejection fraction score. A total of 76 patients had an age, creatinine, and left ventricular ejection fraction score of ≤1.17 (Group I) and 38 patients had an age, creatinine, and left ventricular ejection fraction score of >1.17 (Group II). The number of patients with severe lesions in fractional flow reserve was significantly higher in Group II compared with Group I (60.5 vs. 32.9%, p=0.005). According to the Kaplan-Meier analysis, a significant increase was observed in major adverse cardiac events and mortality during the follow-up period in the group with a high-risk score (Log Rank: 15.01, p<0.001 and Log Rank: 8.51, p=0.004, respectively). In light of the data we obtained from our study, we found a correlation between the severity of the lesion detected in fractional flow reserve and the age, creatinine, and left ventricular ejection fraction scores. In addition, we found that patients with high age, creatinine, and left ventricular ejection fraction scores had higher mortality and major adverse cardiac events rates during follow-up.

High Dose Methylprednisolone versus Low Dose in Correction of Congenital Acyanotic Heart Disease

ABSTRACT Background A large number of pediatric patients undergoing congenital heart disease corrective procedures receive peri-operative corticosteroids, aiming to reduce post-operative inflammation and capillary leak following cardiopulmonary bypass (CPB). This study aimed to compare the effect of different doses of methylprednisolone on inflammatory mediators’ production and effect on myocardium. Methods A trial was conducted on pediatric patients undergoing surgical correction for congenital acyanotic lesion needing CPB machine. Patients were divided into 3 groups: group A patients received 10 mg/kg methylprednisolone (MP) after induction, group B received 30 mg/kg MP and group C patients received placebo. Results Serial measurement of serum troponin, IL6 and random blood sugar showed no differences in the 3 studied groups at the first measurement, and random blood glucose at ICU admission and hour-24 were highest in the high-dose group (IL6 was lowest) with P value <0.001. Troponin showed no difference at ICU admission, while at hour-24, it was lowest in the high-dose group with p value<0.001, followed by the low-dose group and the highest in control. The ejection fraction (EF) at hour-6 was highest in the high-dose group with p value<0.001, followed by the low-dose group and lowest in control. The vasoactive inotrope score was lowest in high-dose followed by low-dose groups followed by control. As regards complications, there was no different significance between groups. Conclusion High-dose MP (30 mg/kg) given to pediatric patients undergoing surgical correction of congenital acyanotic heart disease showed better outcomes such as less elevation of inflammatory mediators, lower level of troponin, vasoactive score and higher ejection fraction, with no additional complications recorded.

The long-term benefit of a cardiac rehabilitation program after myocardial infarction in patients under the Managed Care for Acute Myocardial Infarction Survivors (MACAMIS) program in Poland: A single-center study.

The Managed Care for Acute Myocardial Infarction Survivors (MACAMIS) program introduced for patients after myocardial infarction (MI) consists of 4 modules including early cardiac rehabilitation (CR). We compared the impact of CR on survival of patients after MI included in the MACAMIS program. Patients in MACAMIS were divided into subgroups based on being qualified or not qual-ified for CR and on whether they completed or failed to complete CR. We evaluated one-, two-, and three-year mortality. Of 244 patients in MACAMIS, 174 patients were qualified for CR. They were younger, had less advanced coronary artery disease (CAD), higher ejection fraction (EF), and fewer comorbidities. Finally, 102 (58.6%) patients completed CR. These patients were younger and more likely to have STEMI; they were more often treated invasively, with no differences in comorbidity burden. The survival rates at one, two, and three years were 93.6%, 87.8%, and 65.0%, respectively. Patients who qualified for CR had a better prognosis. The mortality rates at one, two, and three years were 2.38% vs. 16.18% (P = 0.0003), 6.71% vs. 25.4% (P = 0.002), and 26.87% vs. 51.35% (P = 0.01), respectively. Patients who completed CR, again, had a significantly better prognosis. The mortality rate was 1% vs. 10.29% (P = 0.009), 4.17% vs. 17.56% (P = 0.002), and 23.33% vs. 40.54% (P = 0.09) in analyzed periods. The only independent factors related to survival were completion of CR and number of comorbidities. Patients with MI in the MACAMIS program had better prognosis when participating in CR. After completing the MACAMIS program, increased mortality was observed in the following years. Despite the flexibility of the CR program, the proportion of patients who qualified and completed CR remained low.

Prediction of the Outcome of Pakistani Heart Failure Patients by Various Supervised Machine Learning Methods

Aim: To foresee the outcome of heart failure(HF) in Pakistani patients with potential predictors and through various machine learning (ML) methods. Study design:The secondary data of Pakistani patients is taken from the UCI repository in which a cross-sectional, analytical study was planned. Place and duration: This data was collected in April-December, 2015 at the Institute of Cardiology and Allied hospital Faisalabad-Pakistan. Methodology: The data set consisted of299 patients distributed among male (194) and female patients (105). Ages, serum sodium (SS), serum creatinine (SC), gender, smoking, high blood pressure (HBP), ejection fraction (EF), anemia, platelets, Creatinine Phosphokinase (CPK), and diabetes were considered as the potential predictors for predicting the outcome of HF.The data set was analyzed with the help of various machine learning (ML) predictive models including Logistic regression (LR), K-nearest neighbor (KNN), and Decision trees (DT). Results: The ages of the patients were within 60.833±11.894 years. Out of 299 patients, 129 were anemic, 105 had high blood pressure (HBP), and 96 had a smoking history. A statistical model was estimated by applying LR which assisted us in identifying the significant predictors. The sensitivity of the LRwas observed to be 92.1%, whereas 85.6% of the outcome of HF patients was correctly predicted by this model (LR) and DT achieved89.6% prediction accuracy. Conclusion:Since HF is a substantial reason for deaths in Pakistan. Therefore, the identification of its potential risk factors and its accurate prediction by some modern tools are highly demanded. This study applied ML tools for the said task and concluded that among all the fitted ML models, DT predicted the correct outcome for HF patients proficiently. Keywords: Heart failure, machine learning, logistic regression, k-nearest neighbor, decision trees

Sex Differences in Characteristics, Outcomes, and Treatment Response With Dapagliflozin Across the Range of Ejection Fraction in Patients With Heart Failure: Insights From DAPA-HF and DELIVER.

Sodium-glucose cotransporter-2 inhibitors have emerged as a key pharmacotherapy in heart failure (HF) with both reduced and preserved ejection fraction. The benefit of other HF therapies may be modified by sex, but whether sex modifies the treatment effect and safety profile of sodium-glucose cotransporter-2 inhibitors remains unclear. Our analyses aim to assess the effect of sex on the efficacy and safety of dapagliflozin. In a prespecified patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), clinical outcomes were compared by sex (including the composite of cardiovascular death or worsening HF events, cardiovascular death, all-cause death, total events [first and recurrent HF hospitalization and cardiovascular death], and Kansas City Cardiomyopathy Questionnaire scores) across the spectrum of left ventricular ejection fraction. Of a total of 11 007 randomized patients, 3856 (35%) were women. Women with HF were older and had higher body mass index but were less likely to have a history of diabetes and myocardial infarction or stroke and more likely to have hypertension and atrial fibrillation compared with men. At baseline, women had higher ejection fraction but worse Kansas City Cardiomyopathy Questionnaire scores than men did. After adjustment for baseline differences, women were less likely than men to experience cardiovascular death (adjusted hazard ratio, 0.69 [95% CI, 0.60-0.79]), all-cause death (adjusted hazard ratio, 0.69 [95% CI, 0.62-0.78]), HF hospitalizations (adjusted hazard ratio, 0.82 [95% CI, 0.72-0.94]), and total events (adjusted rate ratio, 0.77 [95% CI, 0.71-0.84]). Dapagliflozin reduced the primary end point in both men and women similarly (Pinteraction=0.77) with no sex-related differences in secondary outcomes (all Pinteraction>0.35) or safety events. The benefit of dapagliflozin was observed across the entire ejection fraction spectrum and was not modified by sex (Pinteraction>0.40). There were no sex-related differences in serious adverse events, adverse events, or drug discontinuation attributable to adverse events. In DAPA-HF and DELIVER, the response to dapagliflozin was similar between men and women. Sex did not modify the treatment effect of dapagliflozin across the range of ejection fraction.

Differences in patterns of progression of secondary mitral regurgitation.

Little data exist about the natural history and disease progression of secondary mitral regurgitation (SMR). We sought to study the temporal progression of left-sided volumes and functions in patients who progress to develop severe SMR. We screened patients with chronic severe SMR who had at least one previous transthoracic echocardiography showing non-severe MR. Unsupervised phenotypic clustering based on baseline and rate of change in left ventricular (LV) and left atrial (LA) volumes, ejection fraction (EF), and MR severity progression identified two different phenotypes. We then compared them in terms of clinical characteristics, mechanistic and anatomical features, management, and outcomes. A total of 257 patients were included. Cluster 1 started with lower EF and LA strain and higher LV and LA volumes compared with Cluster 2, with a slower progression into severe SMR. At the onset of severe MR, Cluster 2 still had higher EF, lower LV volumes, but similar LA volumes and strain, and less proportionate SMR, compared with Cluster 1. They also had higher tenting height and more compensatory leaflet growth. On follow-up, Cluster 1 had more ventricular-directed therapies, whereas Cluster 2 received more mitral valve interventions. While the heart failure burden was higher in Cluster 1, there was no difference in mortality rates. Based on disease progression, two distinct progression patterns of SMR exist, having different anatomical and mechanistic features with variation in management and outcomes.

Hemodynamic and Echocardiographic Predictors of Mortality in Pediatric Patients on Venoarterial Extracorporeal Membrane Oxygenation: A Multicenter Investigation

Venoarterial extracorporeal membrane oxygenation (ECMO) supports patients with advanced cardiac dysfunction; however, mortality occurs in a significant subset of patients. The authors performed a multicenter, prospective study to determine hemodynamic and echocardiographic predictors of mortality in children placed on ECMO for cardiac support. Over 8years, six heart centers prospectively assessed echocardiographic and hemodynamic variables on full and minimum ECMO flow. Sixty-three patients were enrolled, ranging in age from 1day to 16years. Hemodynamic measurements included heart rate, vasoactive inotropic score, arteriovenous oxygen difference, pulse pressure, and lactate. Echocardiographic variables included shortening fraction, ejection fraction (EF), right ventricular fractional area change, outflow tract Doppler-derived stroke distance (velocity-time integral [VTI]), and degree of atrioventricular valve regurgitation. Patients were stratified into two groups: those who were able to wean within 48hours of assessment and survived without ventricular assist devices or orthotopic heart transplantation (successful wean group) and those with unsuccessful weaning. For each patient, variables were compared between full and minimum ECMO flow for each group. Thirty-eight patients (60%) formed the unsuccessful group (two with ventricular assist devices, four with orthotopic heart transplantation, 24 deaths), and 25 constituted the successful wean group. At minimum flow, higher EF (53±16% vs 40±20%, P=.0094), less mitral regurgitation (0.8±0.9 vs 1.4±0.9, P=.0329), and lower central venous pressure (12.0±3.9 vs 14.7±5.4mm Hg), along with higher VTI (9.0±2.9 vs 6.8±3.7cm, P=.0154), correlated successful weaning. A longer duration of ECMO (8 vs 5days, P<.0002) was associated with unsuccessful weaning. Multivariate logistic regression predicted minimum-flow EF and VTI to independently predict successful weaning with cutoff values by receiver operating characteristic analysis of EF > 41% (area under the curve, 0.712; P=.0005) and VTI > 7.9cm (area under the curve, 0.729; P=.0010). Diminished VTI or EF during ECMO weaning predicts the need for orthotopic heart transplantation or ventricular assist device support or death in children on ECMO for cardiac dysfunction. Increased postwean central venous pressure or mitral regurgitation along with a prolonged ECMO course also predicted these adverse outcomes. These measurements should be used to help discriminate which patients will require alternative methods of circulatory support for survival.

Characterizing left ventricular stiffness in women with signs and symptoms of ischemia with no obstructive coronary arteries

Abstract Background Women with signs and symptoms of ischemia and no obstructive coronary arteries (INOCA) have evidence of diastolic dysfunction and are at increased risk of developing heart failure with preserved ejection fraction (HFpEF). However, mechanisms contributing to HFpEF development are poorly understood and often attributed to underlying cardiovascular risk factors. Purpose To compare clinical, invasive, and imaging parameters in women with suspected INOCA and various degrees of left ventricular (LV) stiffness (as measured by invasive end-diastolic pressure [EDP]/end diastolic volume [EDV]). Methods Women with suspected INOCA underwent invasive LV pressure-volume loop analysis at rest and coronary function testing with a Doppler wire in the left anterior descending artery. Intracoronary vasoactive substances (adenosine, acetylcholine, nitroglycerin) were infused into the left main artery, as published. Rest and adenosine stress cardiac magnetic resonance (CMR) imaging was performed to evaluate LV function, structure, perfusion, and fibrosis. Women in different tertiles of EDP/EDV ratio were compared using t-tests. Results A total of 62 women with complete invasive data were included; 2 did not complete CMR. Compared to the lower EDP/EDV tertile, women in the upper tertile were older, had higher ejection fraction, higher mass/volume ratio, worse diastolic function, greater aortic stiffness and worse coronary microvascular function (Table 1). Traditional cardiovascular risk factors were not significantly different. Conclusion Among women with INOCA, older age, coronary microvascular dysfunction, and aortic stiffness were related to greater LV stiffness at rest. Those with the highest EDP/EDV ratio had hyperdynamic LV systolic function and the smallest LV size. More work is needed to understand contribution of coronary microvascular dysfunction to HFpEF progression. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): National Institutes of HealthErika Glazer Women's Heart Health Project

Effect of Dapagliflozin on Cause-Specific Mortality in Patients With Heart Failure Across the Spectrum of Ejection Fraction

In 2 trials enrolling patients with heart failure (HF) across the spectrum of ejection fraction (EF), dapagliflozin has been shown to reduce the rate of the composite of worsening HF events or death from cardiovascular (CV) causes. To examine the effects of dapagliflozin on cause-specific CV and non-CV mortality across the spectrum of EF. This was a participant-level, pooled, prespecified secondary analysis of data from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure, or DAPA-HF trial (participant left ventricular EF [LVEF] ≤40%), and Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure, or DELIVER trial (participant LVEF >40%), to assess the effects of randomized treatment on cause-specific mortality. The trials assigned adjacent populations of patients with chronic HF, New York Heart Association class II-IV symptoms, and elevated natriuretic peptides to treatment with dapagliflozin (10 mg, once daily) or placebo. The primary outcome for each study was a composite of worsening HF events (hospitalization or urgent heart failure visits) or CV death. Clinical outcomes, including all deaths, were adjudicated as to cause by clinical end points committees blinded to treatment assignment. Dapagliflozin vs placebo. The mode of death in relation to baseline EF was examined, as well as the effect of randomized treatment on cause-specific death in Cox regression models. Relationships with continuous EF were modeled using Poisson regression. Of 11 007 patients in the pooled data set, there were 1628 deaths during follow-up (mean [SD] age, 71.7 [10.3] years; 1139 male [70.0%]). Of those who died, 872 (53.5%) were ascribed to CV deaths, 487 (29.9%) to non-CV deaths, and 269 (16.5%) to undetermined causes. Of CV deaths, 289 (33.1%; this represented 17.8% of total deaths) were due to HF, 441 (50.6%; 27.1% of total deaths) were sudden, 69 (7.9%; 4.2% of total deaths) were due to stroke, 47 (5.4%; 2.9% of total deaths) to myocardial infarction, and 26 (3.0%; 1.6% of total deaths) were due to other CV causes. The proportion of non-CV deaths was higher in those with higher EF. In the pooled population, across the spectrum of EF, treatment with dapagliflozin was associated with lower rates of CV death (hazard ratio [HR], 0.86; 95% CI, 0.75-0.98; P = .02), principally due to lower rates of sudden death (HR, 0.84; 95% CI, 0.70-1.01; P = .07) and HF death (HR, 0.88; 95% CI, 0.70-1.11; P = .30), with little difference in rates of death from stroke or MI. In a pooled analysis of patients with HF in the DAPA-HF and DELIVER randomized clinical trials, across the full spectrum of LVEF, dapagliflozin significantly reduced risks of CV death with contributions from lower rates of sudden death and death from progressive HF. ClinicalTrials.gov Identifier: NCT03036124, NCT03619213.