During the four-year follow-up period, 19% of STEMI patients experienced a MACE, involving 15% from non-LV remodelers and 34% from LV remodelers (p = 0.01). The cut-off values for baseline GWI of 1680 mmHg% and baseline GWE of 84% had the best accuracy in predicting MACEs. In conclusion, non-invasive myocardial work indices offered a reproducible and accurate method to predict post-MI LV remodeling and MACEs.The goal of this study was to assess whether subtle changes in myocardial work indices may predict left ventricular (LV) remodeling and major cardiac events (MACEs) in patients with a first ST-elevation acute myocardial infarction (STEMI) and preserved LVEF after successful myocardial revascularization with PCI. Methods. Consecutive STEMI patients in sinus rhythm and with an LV ejection fraction ≥ 50% following a successful PCI were recruited. Conventional and two-dimensional speckle tracking echocardiography (2D-STE) was conducted within 36 h of the PCI and 3 months later. Patients having an increase of more than 20% in LV diastolic volume were included in the LV remodeling group. MACEs were noted throughout a four-year period of follow-up. Results: The study comprised 246 STEMI patients with a mean age of 66; 72% of whom were men. In 24% (58) of the patients, LV remodeling developed. These patients were older, more frequently hypertensive, and had a smoking history. They also exhibited significantly lower baseline and 3-month values for the myocardial global index (GWI), global constructive work (GCW), and global myocardial efficiency (GWE). The cut-off values of 1670 mmHg% for GWI and 83% for GWE were predictive of LV remodeling ( After an acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI), left ventricular (LV) remodeling is a key predictor of both short-term and long-term major cardiac adverse events (MACEs) . It is cConventional echocardiography is the recommended method for identifying HF in patients with AMI by assessing the LV ejection fraction (EF) and the wall motion score index . LV straMyocardial work (MW) imaging employing 2D-STE is a sensitive tool for detecting localized wall motion abnormalities as well as a strong method for measuring myocardial performance beyond LVEF ,7. It asThe objective of this research was to assess whether subtle abnormalities of myocardial work indices may predict LV remodeling and MACEs in subjects with a first acute ST-elevation myocardial infarction (STEMI) and preserved LVEF after efficient myocardial revascularization with PCI.This is a case-control prospective research that included consecutive patients admitted with a first STEMI between January 2018 and May 2019, in sinus rhythm and with an LVEF ≥ 50% after an efficient primary PCI performed within 12 h of symptoms beginning.Patients with unsatisfactory echocardiographic images, previous myocardial infarction, cardiac pacemaker/defibrillator, open-chest surgery, moderate or severe mitral regurgitation, moderate or severe aortic stenosis, severe chronic renal failure, liver disease, and non-cardiac diseases with a life expectation below a year, have been excluded from the research.The study was performed at the Cardiology Departments of the Clinical Emergency Municipal Hospital and the Institute of Cardiovascular Disease in Timisoara. Conventional and 2D-STE were carried out at baseline (within 36 h following the PCI) and at 3 months after the event.Corresponding to the LV diastolic volume (DV) at baseline and at 3 months following the STEMI, the patients were split into two groups: group A (without LV remodeling) and group B (with LV remodeling). LV remodeling was described as an increase of ≥20% of LVDV from enrollment [The patients were monitored for a period of 4 years and the following endpoints were recorded as MACEs: cardiovascular mortality, myocardial revascularization by PCI or aorto-coronary by-pass grafting (CABG), and hospitalizations for heart failure.The Ethics Commission of Timisoara’s “Victor Babes” University of Medicine and Pharmacy agreed with the research (nr 36/2017). According to the Helsinki Declaration, all patients completed an informed consent form to participate in the research.Data regarding sex, age, heart disease risk factors , clinical exam information, laboratory data, 12 leads—resting electrocardiogram, 2D-transthoracic echocardiography, and coronary angiography results were obtained from the patients’ records at admission for the STEMI.STEMI was confirmed if at least two of the subsequent conditions occurred: (1) typical angina exceeding 20 min; (2) ST-segment elevation of ≥1 mV continuing for more than 0.08 s in at least two adjacent leads; (3) transitory enhancement in cardiac enzymes to more than twofold the normal level .The STEMI patients were assigned to a Killip class based on their clinical presentation: no heart failure, class 1; moderate heart failure, class 2; acute pulmonary edema, severe heart failure, class 3; and cardiogenic shock, class 4 .At admission, peripheral plasma probes were obtained. A Modular Analytics E170 NT-proBNP immunoassay  was used. Standard biochemical tests were performed throughout the hospital stay, including hemoglobin, glycated hemoglobin, creatinine, potassium, sodium, LDL cholesterol, and creatin-phosphokinase MB. To determine the predicted rate of glomerular filtration, the Modification of Diet in Renal Disease (MDRD) formula was utilized .The PCI was accomplished in accordance with the acknowledged techniques after the STEMI was confirmed during the first 12 h from the beginning of symptoms. The standard procedure for treating the culprit lesion involved using a balloon for pre-dilatation and insertion of drug-eluting stents. Significant stenosis was defined as more than 75% in the circumflex, right, and anterior descending coronary arteries or more than 50% in the left main coronary trunk. Multivessel coronary artery disease (CAD) was diagnosed when significant stenosis was found in more than one coronary artery. A PCI was determined to be successful when a TIMI flow 3 was obtained .Within 36 h of the PCI, a baseline echocardiogram was performed in the hospital utilizing a GE Vivid E7 ultrasound system . A second echocardiography test was performed three months following the first one.Simpson’s biplane approach, as endorsed by the American Society of Echocardiography  was usedThe 2D-STE method was applied to evaluate LV distortion models . The EchWe stated the systolic blood pressure value and developed non-invasive myocardial work indices, which are the product of segmental shortening velocity and momentary LV pressure. The entire LV work during systole is determined by the global myocardial work index (GWI). Myocardial constructive work (GCW) estimates all the work contributing to pump function (systolic shortening in addition to isovolumic relaxation). Global wasted work (GWW) estimates the amount of work that does not provide ejection . The ratio of GCW to the total of GCW plus GWW is used to determine global work efficiency (GWE). The pressure-strain loop diagram is utilized for determining global MW, whereas the GCW and GWW parameters are determined from the contraction pattern of regional segments ,20.Categorical variables were represented using numbers and percentages. According to Kolmogorov-Smirnov tests, continuous variables normally distributed were presented as means with a standard deviation of 1, whereas those non-normally distributed were given as median .p < 0.05 values were regarded as statistically notable.For continuous and regularly distributed values, the paired t-test was used to compare the subject groups. The Mann-Whitney U-test was used to compare continuous non-normally distributed variables, and the chi-squared test was used to compare categorical variables. The odds ratio (OR) and confidence interval (CI) of many factors associated with LV remodeling and MACEs were determined using univariate analysis. The univariately significant factors linked to LV remodeling were included in a multivariate analysis, using a backward stepwise logistic regression model. The independent variables identified by multivariate logistical regression were analyzed using the receiver operating characteristic (ROC) to determine their accuracy. For survival analyses, the Kaplan-Meier procedure was utilized. We utilized the MedCalc Statistical Software version 22.003  for statistical analysis. Two-tailed Seventeen of the 263 STEMI patients that were enrolled at start-up were excluded and not analyzed . Finally, 246 patients aged 31 to 79 years (mean age 66 ± 13 years) were enrolled in the research, including 178 (72%) men.At the 3-month echocardiographic evaluation, we found that 58 (24%) of the patients had LV remodeling . The stup = 0.16).The study reveals that there were no significant disparities among the groups with respect to the localization of the culprit’s vessel. However, the LV remodeling group exhibited a higher proportion of multi-vessel coronary artery disease. Furthermore, it was observed that the initial patency of the infarct-related artery was present in 44 (18%) of the STEMI patients, with a greater frequency in the non-remodelers in comparison to the remodelers, although this contrast was not deemed statistically substantial (p < 0.0001) and higher GWW (p = 0.001). After 3 months, they presented significantly lower LVEF p < 0.0001), higher LVDV (p = 0.03), higher LV systolic volume (p = 0.01), and higher wall motion score index (p < 0.01). Their myocardial work indices revealed significantly lower GWI, GWE, and GCW and higher GWW (p < 0.01) compared to the non-remodelers.The echocardiographic data are shown in According to p < 0.04) and the AUC for the Killip class (p < 0.0001). The analysis of the ROC curves showed that the cut-off values predictive of LV remodeling were a baseline GWE ≤ 83% , a baseline GWI ≤ 1670 mmHg% , and a Killip class > 2 .The most powerful predictor of LV remodeling was baseline GWE (%), with an area under the curve (AUC) of 0.95, significantly higher than the AUC of the ROC curve for GWI (p = 0.01). In addition, 29 (12%) patients were hospitalized for heart failure, and 15 (6%) suffered a new myocardial revascularization by a PCI. No patient died. The hospitalization rate was 9% in group A, and 19% in group B (p = 0.03). The myocardial revascularization rate was 4% in group A and 12% in group B (p = 0.02). The Kaplan-Meier survival curve for MACEs is presented in p < 0.01).Throughout the 4-year follow-up period, 48 patients (19%) suffered a MACE, 28 (15%) from the non-remodelers and 20 (34%) from the LV-remodelers . We found no table differences when comparing these AUCs with the AUCs of the ROC curves for peak CK-MB (p < 0.01) and Killip class (p < 0.04).The most powerful predictors of MACEs were baseline GWE and baseline GWI, with no significant difference between the AUCs of their ROC curves (p < 0.001), baseline GWE ≤ 84% , baseline CK-MB > 236 IU/L  and Killip class > 2 .Analyzing the ROC curves, we found the following cut-off values associated with the occurrence of MACEs: baseline GWI ≤ 1680 mmHg%  LV remodeling and the incidence of MACEs during a 4-year follow-up period.All the study patients had a TIMI flow of 3 in the culprit lesion vessel, which is a good sign. Additionally, their LVEF was over 50% after the primary PCI. These parameters indicate that the treatment has been successful and that the included patients have a low risk of developing LV remodeling .Several studies have revealed that a significant proportion, approximately 10–20%, of patients diagnosed with STEMI display spontaneous coronary recanalization before angioplasty . This phWe considered it crucial to continue monitoring these patients to ensure continued improvement in their condition. This ongoing monitoring is essential to guarantee that they are receiving the best possible care and treatment and to make any necessary adjustments to their care plan to ensure a successful outcome.The post-infarction remodeling of the left ventricle is a complex process that can have serious implications for patients. This remodeling typically involves an increase in both systolic and diastolic left ventricular volumes, which can indicate a poor prognosis for recovery. One common definition of this remodeling is an increase in end-diastolic left ventricular volume by 20% at 6 months after MI compared with the baseline, although early remodeling can be diagnosed as early as one month after the MI . Our teap < 0.001).Our study demonstrates that noninvasive myocardial work indices provide valuable data for the identification of STEMI patients with a risk of experiencing LV remodeling and major cardiac events. We found that the STEMI patients who developed early LV remodeling presented more severe impairment of all MW indices at baseline. The 3-month follow-up examination showed that, with the exception of GWW, all MW indices improved, but still remained significantly lower than in the patients without LV remodeling  LV remodeling . LustosaIn the current study, noninvasive myocardial work indices were measured within 36 h after the primary PCI in STEMI patients and after 3 months. We also found that the patients who developed early LV remodeling presented lower baseline values of myocardial work indices compared with their counterparts. These differences are probably explained by the larger ischemic area, and consequently, the more dispersed metabolic changes that can be successfully identified by myocardial work. During myocardial ischemia, the heart reduces the synthesis of adenosine triphosphate due to alterations in metabolism. Russell et al. demonstrated the association between MW indices and glucose metabolism by positron emission tomography using 18F-fluorodeoxyglucose .p < 0.001). Our research findings suggest that cut-off values of ≤1670 mmHg% for GWI and ≤83% for GWE can accurately predict early (within 3 months) LV remodeling, with a significant p-value of <0.0001. These findings are crucial in identifying patients at risk for LV remodeling, enabling early intervention and better outcomes.At the 3-month evaluation, GWI, GCW, and GWE increased in both patient groups, but the values remained significantly lower in the patients who developed LV remodeling (Low baseline GWI and GWE were also significant independent predictors for the occurrence of a MACE during the 4-year follow-up period. In our study, the cut-off values of a baseline GWI ≤ 680 mmHg%, and a baseline GWE ≤ 84% showed the highest accuracy in predicting long-term MACEs in STEMI patients. Based on the findings of Coisne et al.’s study, patients with STEMI and NSTEMI who have a GWE below 91% are at a higher risk of experiencing poor outcomes within 2 years of monitoring . InteresEvidence suggests that revascularization procedures offer great benefits in terms of improving survival rates in STEMI patients. However, not all myocardium can experience improvement through revascularization. Studies have shown that even after successful revascularization of infarct-related arteries, there is still a relatively high incidence of microvascular obstruction or coronary microvascular dysfunction . To deteAccording to our results, GWE and GWI seem to be accurate non-invasive echocardiographic parameters of myocardial function to predict early LV remodeling and adverse outcomes after an AMI. They should be used to optimize medical treatment and compliance, correct modifiable cardiovascular risk factors, and investigate for residual myocardial ischemia.Our study has several limitations. The research was conducted in only one interventional cardiology center, and the sample size of STEMI patients was relatively small due to the inclusion criteria. When assessing myocardial work through pressure-strain loops, we calculated LV pressure using cuff sphygmomanometer data. However, it’s important to note that these non-invasive measurements have known limitations that should be taken into consideration. This method involves the measurement of systolic blood pressure, which serves as an estimation of LV pressure, under the assumption that there is no LV outflow obstruction. Patients having a poor echocardiographic window during the index admission were excluded, which may have caused bias in the selection process. Cardiac magnetic resonance imaging or single-photon emission computed tomography myocardial perfusion was not accessible for measuring the infarct dimension. More research is required to investigate the predictive value of non-invasive myocardial indices in STEMI patients.Non-invasive myocardial work indices represent a repeatable and accurate examination method to measure LV performance. Among them, GWI and GWE may be the most suitable predictors of early LV remodeling and MACEs in STEMI patients with preserved LVEF following an efficient primary PCI.


An elevated heart rate at admission or discharge is known to be associated with poor cardiovascular outcomes in patients with acute myocardial infarction (AMI). The association between post-discharge average office-visit heart rate and cardiovascular outcomes in patients with AMI has rarely been studied. We analyzed data for 7840 patients from the COREA-AMI registry who had their heart rates measured at least three times after hospital discharge. The office-visit heart rates were averaged and categorized into four groups by quartiles . The primary end point was a composite of cardiovascular death, myocardial infarction, and ischemic stroke. During a median of 5.7 years of follow-up, major adverse cardiovascular events (MACE) affected 1357 (17.3%) patients. An average heart rate higher than 80 bpm was associated with an increased incidence of MACE compared to the reference average heart rate of 68–74 bpm. When dichotomized into <74 or ≥74 bpm, a lower average heart rate was not associated with MACE in patients with LV systolic dysfunction, in contrast to those without LV systolic dysfunction. An elevated average heart rate at office visits after AMI was associated with an increased risk of cardiovascular outcomes. Heart rate monitoring at office visits after discharge provides an important predictor related to cardiovascular events. Heart rate was determined to be a risk factor for mortality and morbidity in various cardiovascular diseases, including hypertension , heart fGuidelines recommend that beta-blocker treatment should be considered for patients with AMI, unless the patients are in Killip class III or higher, and have cardiogenic shock ,9. Beta-Thus, we sought to assess the association between heart rate during follow-up and cardiovascular outcomes in a real-world AMI registry to determine the optimal heart rate after acute myocardial infarction.n = 2325), and those who died in the hospital (n = 554) were excluded. Thus, 7840 patients who had their heart rate measured at least 3 times after discharge were analyzed. Patients were categorized into four groups according to quartiles of average heart rate values.Between January 2004 and April 2015, a total of 10,719 patients with AMI were registered in the Convergent Registry of Catholic and Chonnam University for Acute MI (COREA-AMI), which was designed to investigate real-world outcomes in all-comers with AMI. According to electrocardiography findings, the clinical diagnosis was divided into ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). The COREA-AMI I registry has been previously reported on, and has included patients with AMI who underwent PCI from January 2004 to December 2009. The COREA-AMI II registry added additional patients from January 2010 to August 2014. The current registry comprised updated new clinical and angiographic parameters and evaluated long-term clinical data for as long as possible until 2019. Patients were followed at 6 months after enrollment (PCI date), and every year thereafter. Their heart rates were collected from medical records of office visits, and were measured by automated blood pressure devices. The timing of the first office-visit heart rate measurement was 6 months after the index procedure (PCI), and every year thereafter. Coronary angiography and primary percutaneous coronary intervention (PCI) were performed according to the current standard guidelines. Antiplatelet therapy and peri-procedural anticoagulation were administered according to standard regimens. All patients were prescribed aspirin (loading dose 200 mg) plus P2Y12 inhibitors, such as clopidogrel (loading dose 300 or 600 mg), ticagrelor (loading dose 180 mg) or prasugrel (loading dose 60 mg), before or during PCI. Predilation, direct stenting, postadditional balloon inflation, thrombus aspiration and administration of glycoprotein IIb/IIIa receptor blockers were performed at the discretion of individual interventional cardiologists. After the procedure, dual antiplatelet therapy was maintained for 1 year, and after that, the antiplatelet regimen was selected according to the balance of ischemic and bleeding risk. The necessity of beta-blocker treatment was decided by the physicians in each case. The dosage or the continuation of the use of beta-blocker treatment was left at the discretion of physicians. The post-intervention medications also included statins and renin-angiotensin-aldosterone blockers.The primary endpoint was a composite of cardiovascular death, myocardial infarction, and ischemic stroke. The secondary endpoints were individual components of the primary endpoint. All deaths were considered to be cardiovascular deaths unless a definite non-cardiac cause could be clearly identified. Myocardial infarction was defined as an elevated cardiac marker(s) with clinical evidence of ischemia, such as symptoms of myocardial ischemia, new ischemic electrocardiographic changes, and development of pathologic Q waves. Ischemic stroke was defined as the presence of a new focal neurologic deficit thought to be vascular in origin, with signs or symptoms lasting more than 24 h. For all composite outcomes, we analyzed the number of patients with at least one event from the composite outcomes. Patients with more than one contributing event were only counted once. The study protocol was approved by the ethics committee at each participating center, and was followed according to the principles of the Declaration of Helsinki. All patients provided written informed consent.Baseline characteristics are described as the mean ± standard deviation for continuous variables, and as the absolute number and percentage for categorical variables. Heart rates are expressed as a continuous variable, or averaged and categorized into four groups by quartiles ). Differences in baseline characteristics between the different quartiles of average heart rate were evaluated using a one-way analysis of variance for continuous variables, and chi-square tests for categorical variables. Major adverse cardiovascular outcomes (MACE) were defined as cardiovascular death, myocardial infarction, and ischemic stroke. Multivariable analysis was performed to assess the prognostic value of an average heart rate and MACE after adjusting for sex, age, BMI, Killip class, hypertension, diabetes, previous MI, previous PCI, peripheral artery disease, end-stage renal disease, chronic lung disease, and left-ventricular systolic dysfunction (defined as a left-ventricular ejection fraction of less than 40%). Hazard ratios (HRs) were estimated with multivariable adjusted Cox proportional hazards models using the group with heart rates of 68–74 bpm as a reference. Survival curves were constructed with Kaplan–Meier estimates by groups for the primary composite end points and individual components of MACE. The groups were compared using the log-rank test for time-to-event data with respect to cardiovascular death, myocardial infarction, and ischemic stroke. Time-to-event was the duration between the index procedure (PCI) and the occurrence of the clinical events. The unadjusted and adjusted relationships between heart rate and primary outcomes were also assessed using a time-dependent Cox PH model with restricted cubic splines. We calculated hazard ratios for average heart rate (a heart rate of 74 bpm or greater) within each subgroup using Cox PH models. The cutoff of 74 bpm was selected as the median average heart rate in the study population.p value of 0.05 was considered to be statistically significant. All statistical analyses were performed with R version 4.0.2 .All statistical tests were two-sided, and a p < 0.001). The mean average heart rate at the office visit was 74 ± 8.42 bpm (interquartile range 68.09–79.29). When patients were categorized into four groups according to the quartiles of average heart rate, there was a significant trend toward a higher average heart rate with diabetes, chronic lung disease, high heart rate at admission and discharge, decreased LV systolic function, and low prescription rate of beta-blockers and renin-angiotensin-aldosterone blockers at discharge. There were no significant differences among the heart rate quartiles with regard to body mass index, hypertension, dyslipidemia, smoking status, end-stage renal disease, and peripheral artery disease. The prescription rate of beta-blockers decreased as the quartile of average heart rate increased .Among the 10,719 patients included in the COREA-AMI registry, data for 7840 patients with heart rate measured at least 3 times after hospital discharge were available. The baseline characteristics of the total patient population are shown in During a median follow-up period of 5.7 years (IQR 3.8–7.6), the primary outcome, which is a composite of cardiovascular death, myocardial infarction, and ischemic stroke, occurred in 1357 patients (17.3%). For the secondary outcomes, cardiovascular death, myocardial infarction, and ischemic stroke occurred in 781 (10.0%), 474 (6.0%), and 272 (3.5%) patients, respectively .Kaplan–Meier curves for average heart rate divided by quartiles and primary outcomes during the follow-up period are shown in p < 0.001). Discharge heart rate was not associated with the risk of MACE in univariate analysis . Compared with the reference group (heart rate 68–74 bpm), the adjusted hazard ratio for the primary outcomes was 0.91  for the heart rate < 68 bpm group, 1.12  for the heart rate of 74–80 bpm group, and 1.39  for the heart rate higher than 80 bpm group. (p < 0.001). In addition, age, BMI, Killip class, hypertension, diabetes, and LV systolic dysfunction were all independently associated with the risk of MACE in patients with AMI who were treated with PCI. Even after applying a restricted cubic spline Cox regression analysis, average heart rate showed a positive linear relationship with the risk of primary outcomes , and the prescription rate of β-blockers was lower. In addition, a higher average heart rate was associated with MACE in patients with heart rate measurements recorded on more than six occasions. The survival period was longer in the group of patients with heart rate measurements recorded on more than six occasions .The average heart rate for the office visits showed significant interactions with LV systolic dysfunction and the number of heart rate measurements . Lower aThe major findings of this study regarding average heart rate and clinical outcomes of acute myocardial infarctions undergoing PCI were as follows: (1) A higher average office-visit heart rate was associated with an increased risk of cardiovascular events in the post-MI period. (2) Cardiovascular mortality and myocardial infarction increased in patients with a higher average heart rate. (3) Average office-visit heart rate had a linear relationship with cardiovascular events. The lower the average heart rate was, the better the clinical outcomes experienced during the post-MI period.In patients with AMI, there were results showing a link to prognosis depending on the heart rate at admission and discharge. Perne et al. suggested that a heart rate >90 bpm at admission reduced survival at 3 months in patients presenting with myocardial infarction in a large German registry . Antoni The oldest biomarker in cardiovascular medicine is resting heart rate. Heart rate is a major determinant of myocardial oxygen demand, and it affects coronary blood flow through diastolic filling time. The prognostic value of heart rate in patients with various heart diseases, including myocardial infarction, hypertension, and heart failure, is well established ,18,19. TIn heart failure, elevated heart rate is considered a physiological and beneficial compensatory response up to a certain point, whereas there might be a direct causative effect on outcomes in coronary disease. Heart rate (measured at rest and during sinus rhythm) has prognostic importance in patients with left-ventricular systolic dysfunction, and changes in heart rate are predictive of outcomes . In contOur study had several limitations. First, the possibility of unobserved confounders and selection bias should be considered because our study was retrospective, observational, and nonrandomized. Second, we did not analyze the type, dose, and achievement rate of the recommended dose of β-blockers. The results may be impacted by these factors. However, in the OBTAIN and KAMIR studies, there was no correlation between the dose of β-blockers and the survival benefit ,14. GiveThese large, real-world data show that elevated average office-visit heart rate is associated with poor clinical outcomes in patients with acute myocardial infarction. Heart rate monitoring at post-discharge office visits provides an important predictor related to cardiovascular events. A higher office heart rate was a risk factor associated with cardiovascular death and recurrent myocardial infarction. Therefore, the thorough tracking of heart-rate changes in outpatients can aid the treatment of patients in the post-MI period.


There is a close relationship between the intestinal microbiota and heart failure, but no study has assessed this relationship in infants with congenital heart disease. This study aimed to explore the relationship between heart failure and intestinal microbiota in infants with congenital heart disease.Twenty-eight infants with congenital heart disease with heart failure admitted to a provincial children’s hospital from September 2021 to December 2021 were enrolled in this study. A total of 22 infants without heart disease and matched for age, sex, and weight were selected as controls. Faecal samples were collected from every participant and subjected to 16S rDNA gene sequencing.Enterococcus, Bifidobacterium, Subdoligranulum, Shigella, and Streptococcus, and the most abundant bacteria in the control group were Bifidobacterium, Blautia, Bacteroides, Streptococcus, and Ruminococcus. The alpha and beta diversities of the gut bacterial community in the heart failure group were significantly lower than those in the control group (p<0.05). Compared with the control group, retinol metabolism was significantly downregulated in the heart failure group.The composition of the intestinal microbiota was significantly disordered in infants with heart failure caused by congenital heart disease compared with that in infants without heart disease. At the phylum level, the most abundant bacteria in the heart failure group were Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes, and the most abundant bacteria in the control group were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. At the genus level, the most abundant bacteria in the heart failure group were Heart failure in infants with congenital heart disease caused intestinal microbiota disorder, which was characterised by an increase in pathogenic bacteria, a decrease in beneficial bacteria, and decreases in diversity and richness. The significant downregulation of retinol metabolism in the intestinal microbiota of infants with heart failure may be related to the progression of heart failure, and further study of the underlying mechanism is needed. Heart failure is the terminal stage of all types of cardiovascular disease and is a common cause of death . The patCongenital heart disease is a deformity caused by disorders of foetal heart and large blood vessel development . It is oThe present study was approved by the ethics committee of our hospital and adhered to the tenets of the Declaration of Helsinki. Additionally, all parents of the patients signed the consent form before participating in the study.This cohort study aimed to explore the relationship between heart failure and the intestinal microbiota in infants with congenital heart disease. A total of 28 infants with heart failure caused by left-to-right shunt congenital heart disease who were admitted to the cardiac surgery department of a provincial children’s hospital in southeast China from September 2021 to December 2021 were enrolled in this study. A total of twenty-two infants without heart disease and matched for age, sex, and weight were selected as controls.Inclusion criteria were infants with heart failure caused by left-to-right shunt congenital heart disease. Exclusion criteria the following: (1) other major organ diseases, such as digestive tract malformation, liver failure, or kidney failure; (2) digestive tract diseases, such as diarrhoea, constipation, or jaundice; (3) infection or receiving antibiotics; and (4) parental refusal to participate in the study.Faecal samples (1 ml) were collected from each patient, immediately frozen in liquid nitrogen, and stored at −80°C.Total genomic DNA samples were extracted using the OMEGA Soil DNA Kit (M5635-02) . DNA extracted from the sample was used as a template. PCR amplification of the bacterial 16S rRNA genes V3–V4 region was performed using the forward primer 338F (5′-ACTCCTACGGGAGGCAGCA-3′) and the reverse primer 806R (5′-GGACTACHVGGGTWTCTAAT-3′ ). The amplified product was purified and recycled by using clean beads. The purified and recycled products were subjected to fluorescence quantitation with a Quant-iT PicoGreen dsDNA Assay Kit in a microplate reader . According to the fluorescence quantitation results, each sample was mixed in proportion according to the sequencing volume requirements of each sample. The sequencing library was prepared with a TruSeq Nano DNA LT Library Prep Kit (Illumina). Finally, paired-end sequencing was carried out on a NovaSeq sequencer with a NovaSeq 6000 SP Reagent Kit (500 cycles).via principal coordinate analysis, non-metric multidimensional scaling, and unweighted pair-group method with arithmetic means hierarchical clustering. Microbial functions were predicted by PICRUSt2 upon MetaCyc and KEGG databases.Microbiome bioinformatics were performed with QIIME2 2019.4 with slight modification according to the official tutorials. Briefly, raw sequence data were demultiplexed using the demux plugin followed by primers cutting with cutadapt plugin. Sequences were then quality filtered, denoised, and merged, and chimera removed using the DADA2 plugin. Venn diagram was generated to visualise the shared and unique ASVs among samples or groups using R package “VennDiagram,” based on the occurrence of ASVs across samples/groups regardless of their relative abundance. Alpha-diversity metrics, such as Chao1 richness estimator, observed species, Shannon diversity index, Simpson index, Faith’s PD, Pielou’s evenness, and Good’s coverage were calculated using the ASV table in QIIME2, and visualised as box plots. Beta diversity analysis was performed to investigate the structural variation of microbial communities across samples using Jaccard metrics, Bray–Curtis metrics, and UniFrac distance metrics, and visualised via the t-test. Continuous variables without a normal distribution were compared via the non-parametric test. Categorical variables were described as integers and percentages, and comparisons between groups were performed using Fisher’s exact test. A p-value <0.05 was considered statistically significant.SPSS 25.0 software was used for statistical analysis. Continuous variables with a normal distribution were expressed as the mean ± standard deviation and were compared A total of 28 infants with heart failure caused by left-to-right shunt congenital heart disease were enrolled as the heart failure group. There were 21 infants with ventricular septal defects, 5 infants with ductus arteriosus defects, and 2 infants with complete endocardial pad defects. The heart failure group comprised 15 male and 13 female infants with a mean age of 2.8 ± 2.9 months, weight of 4.6 ± 1.8 kg, pulmonary artery pressure of 59.8 ± 10.1 mmHg, and NT-proBNP of 4,218.7 ± 3,757.1 pg/ml. Nine of the infants in the heart failure group were exclusively breastfed, 5 were formula fed, and 14 were both breastfed and formula fed. A total of 22 age- and sex-matched children without heart disease served as controls. The control group comprised 12 male and 10 female infants with a mean age of 2.6 ± 1.7 months and weight of 5.1 ± 1.6 kg. Eight of the infants in the control group were exclusively breastfed, 3 were formula fed, and 11 were both breastfed and formula fed. There were no differences in sex, age, weight, or feeding style between the two groups Table 1.To analyse the differences in intestinal microbial species between the heart failure group and control group, a Venn diagram was constructed using the ASV/OTU abundance table, and the number of members in each set was counted according to presence or absence in the ASV/OTU abundance table. The results showed that there were 1,744 (10.9%) ASVs/OTUs that were shared between the heart failure group and the control group, 7,758 (48.48%) ASVs/OTUs unique to the heart failure group, and 6,502 (40.63%) ASVs/OTUs unique to the control group Figure 1Enterococcus (30.3%), Bifidobacterium (13.1%), Subdoligranulum (5.7%), Shigella (3.6%), and Streptococcus (3.1%), and the most abundant bacteria in the control group were Bifidobacterium (24.3%), Blautia (6.0%), Bacteroides (3.3%), Streptococcus (3.0%), and Ruminococcus (2.5%) , Actinobacteria (20.6%), Proteobacteria (10.3%), and Bacteroidetes (3.7%), and the most abundant bacteria in the control group were Firmicutes (47.8%), Proteobacteria (22.1%), Actinobacteria (21.8%), and Bacteroidetes (3.1%). At the genus level, the most abundant bacteria in the heart failure group were s (2.5%) Figure 2The comparison of the alpha diversity of the intestinal microbiota between the two groups showed that the Chao1 and observed species indices were significantly lower in the heart failure group than in the control group Figure 3The beta diversity index focuses on the comparison of diversity between different environments, which are represented by infant groups in the present study. We visually analyse the data using principal coordinate analysis, and differences were further examined using Adonis. The PCoA of beta diversity based on the Bray−Curtis distance matrix revealed that the differences in community composition between the two groups were significant Figure 4The functional properties of the intestinal microbiota were predicted using PICRUSt2. The analysis of Kyoto Encyclopedia of Genes and Genomes pathway annotations at level 2 as determined by PICRUSt2 revealed significant differences in retinol metabolism between the two groups. Compared with the control group, retinol metabolism was significantly downregulated in the heart failure group Figure 5Heart failure is a formidable global public health challenge and is responsible for more than 1 million hospitalisations each year . Heart fThe gut contains trillions of microbes—as many cells as the total number of human cells . The micBacteroides and Bifidobacteria and increases in Firmicutes and Proteus (Candida, Salmonella, Shigella, and Campylobacter in faecal samples from patients with heart failure (Enterococcus, Shigella, and Subdoligranulum in the intestinal tract was significantly higher in infants with congenital heart disease with heart failure, while the proportion of beneficial bacteria such as Bifidobacterium, Blautia, and Bacteroides was significantly lower. Nagatomo et al. and Hooper et al. demonstrated that an increase in pathogenic bacteria and a decrease in beneficial bacteria lead to an increase in inflammatory factors in the intestine and an increase in the body’s inflammatory response, which aggravate the progression of heart failure (Heart failure causes intestinal ischemia or hyperemia, which can result in a reduction in the intestinal oxygen supply. As a result, the intestinal environment changes, which leads to changes in the composition of the intestinal microbiota, mainly a reduction in beneficial intestinal bacteria and an increase in pathogenic bacteria. Chen et al. showed that intestinal microbiota disorder in patients with heart failure manifested as decreases in  Proteus . Pasini  failure . Sandek  failure . A simil failure .The intestinal microbiota coexists with the host. The intestine provides a good colonisation environment for microbes, and the intestinal microbiota plays an important role in maintaining nutrient metabolism, the stability of the intestinal environment, and the health of the body. The intestinal microbiota is the most complex ecosystem in the human body and is composed of a variety of microorganisms residing in the human intestine. These microorganisms coexist mutually in the intestinal tract to jointly maintain the stability of the intestinal environment. Once homeostasis is disrupted, the disorder of the intestinal microbiota will aggravate the pathological state . Kummen Many studies have suggested that retinol metabolism is also involved in the progression of heart failure in infants with congenital heart disease. Yang et al. found that cardiac retinoic acid levels decline in heart failure patients . Osorio There are some limitations to this study. First, the main food of infants is milk. In this study, infants were selected as the participants. Although the influence of some foods on the microbiota has been ruled out, interference from differences in formula and the diets of breastfeeding mothers cannot be ruled out. Second, this study only analyse the intestinal microbiota of infants with left-to-right shunt congestive heart failure and did not analyse other types of heart failure. Third, this study was a single-centre study with a small sample size, and a multicentre study with a large sample size should be conducted next.There is a close relationship between heart failure and the intestinal microbiota in infants with congenital heart disease. Heart failure in infants with congenital heart disease caused intestinal microbiota disorder, which was characterized by an increase in pathogenic bacteria, a decrease in beneficial bacteria, and decreases in diversity and richness. We also found that retinol metabolism of the intestinal microbiota was significantly downregulated in infants with heart failure, which may be related to the progression of heart failure. The underlying mechanism needs to be studied further.https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA862324.The datasets presented in this study are deposited in online repositories. The names of the repositories and accession numbers can be found below: The studies involving human participants were reviewed and approved by Fujian Children’s Hospital. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.Q-LZ designed the study, acquired and interpreted the data, and drafted the manuscript. X-HC analysed and interpreted the data. S-JZ,acquired and analysed the data. J-SH and Y-QL collected and analyse faeces specimens. QC has made substantial contributions to conception and design. HC was involved in analysis and interpretation of data, revision of the manuscript, and given final approval of the version to be published.


The most common organic etiology of mitral regurgitation is degenerative and consists of mitral valve prolapse (MVP). Volume overload because of mitral regurgitation is the most common complication of MVP. Advocating surgery before the consequences of volume overload become irreparable restores life expectancy, but carries a risk of mortality in patients who are often asymptomatic. On the other hand, the post-surgical outcome of symptomatic patients is dismal and life expectancy is impaired. In the present article, we aim to bridge the gap between these two therapeutic approaches, unifying the concepts of watchful waiting and early surgery in a “watchful surgery approach”. The most common etiology is degenerative (DMR) , 2, and On the histological ground, infiltrative or dysplastic tissue disorders characterize MVP, with/without chordal rupture, producing two different phenotypes . At one On the physio-pathological ground, a systolic displacement of one or both mitral leaflets more than 2 mm beyond the plane of the annulus in a long-axis view defines MVP, with or without leaflet thickening. Two-dimensional transthoracic echocardiography (2D-TTE) is the most common diagnostic tool  5). Bas. Bas5). MVP may be syndromic, familial, or isolated (sporadic). We encounter syndromic MVP in connective tissue disorders such as Marfan syndrome, Loeys–Dietz syndrome, Ehlers–Danlos syndrome, pseudoxanthoma elasticum, osteogenesis imperfecta, and aneurysms-osteoarthritis syndrome . Among fSince MVP is associated with such a composed group of underlying conditions and histological characteristics, its outcome is heterogeneous . BesidesIn the present article, we will try to bridge the gap among these two (perhaps only apparently) diverging therapeutic approaches, trying to unify the opposite attitudes of “watchful waiting”  and “ear2.In MVP, the classic auscultatory finding is a dynamic mid-to-late systolic click, frequently associated with a high-pitched, late systolic murmur . A very Systolic flow reversal in more than one pulmonary vein is specific for severe DMR, although eccentric jets can alter flow patterns, even mild or moderate in severity when directed into a pulmonary vein. The jet area or jet area/left atrial area ratio by color flow imaging is valuable as a screening tool to confirm the presence of more than mild DMR, but it is imprecise. This happens particularly in eccentric, wall-impinging jets and in late-systolic ones, as it can occur in MVP .The vena contracta (VC) is the narrowest portion of the regurgitant flow and its measurement represents an approximation of the anatomic regurgitant orifice. A VC width ≥0.7 cm is specific for severe MR and this cut-off can be applied both to central and eccentric jets . As for Concerning quantitative approaches, all methods derive three measures. The effective regurgitant orifice area (EROA) (a measure of lesion severity), the regurgitant volume per beat (RVol) (the severity of volume overload), and the regurgitant fraction (the ratio of the RVol to the forward stroke volume). Measurements of EROA and RVol provide the strongest prognostic information . In mid-3.symptomatic severe DMR regardless of left ventricular (LV) function (Scientific guidelines recommend surgery (class I) in function , 20 and 2, RVol ≥ 15 ml) by exercise echocardiography was associated with reduced symptom-free survival in more than moderate DMR  is common in DMR and is associated with adverse events . Althoug4.4.1.The long-lasting physio-pathological dream in chronic DMR has been to identify the transition of the LV from the compensated phase (when LV is capable of managing the volume overload without permanent consequences if this is relieved by surgery) to the decompensated one (when the consequences of the volume overload are permanent) . In theo2) represents a predictor of increased mortality under conservative management and after surgery  of the LV is an early and sensitive method to detect dysfunction. In asymptomatic chronic DMR, the cutoffs to identify patients at high risk ranges from −17.9% to −21.7% . FurtherBeing ventricular function at rest modestly effective in predicting post-operative ventricular dysfunction, previous studies concentrated on exercise-derived parameters. In asymptomatic DMR, lack of contractile reserve (defined as an increase of 4% of LVEF) strongly predicts postoperative ventricular dysfunction . The abs4.2.2 is a powerful prognostic indicator (2 (diameter > 55 mm)  size is marginally affected by acute changes in preload and afterload, and its remodeling reflects the severity of volume/pressure overload over a longer period , 36. Ourndicator , 38. Acc> 55 mm) , 39. LA > 55 mm) . Among a> 55 mm) . Left at> 55 mm) . The novBesides being an indicator of overload severity, LA size negatively contributes to the outcome of DMR through the occurrence of atrial fibrillation (AFib). As the rhythm progress from sinus to paroxysmal to persistent AFib, the associated risk of mortality increases under non-surgical management, and the positive effects of surgery decrease in magnitude –45. Curr4.3.Pulmonary hypertension (PH) is a common complication of DMR and is related to increased LA pressure due to chronic volume overload. Abnormal pulmonary artery systolic pressure (PASP) independently affects prognosis, by causing right ventricular impairment , and sub4.4.B-type natriuretic peptide (BNP) is released in response to increased myocardial wall stress , 55 and 5.with and without severe DMR  in 4%–7% of young patients undergoing autopsy , 66. Arrvere DMR . Risk faced LVEF . Mitral ced LVEF  69, 70), 70with ced LVEF . The oriced LVEF , 72. In ced LVEF .The stratification of SCD in MAD remains challenging and multiple indicators are currently under investigation. Late gadolinium enhancement localized on the LV infero-basal wall under the posterior leaflet, overlaps with myocardial fibrosis in the autoptic study in SCD victims . The pro6.6.1.early, low-risk, effective and durable repair is associated with lower in-hospital mortality, better survival, and lower long-term morbidity  than after MV replacement (4.7%) . OperatiConcerning durability, the results for anterior and bi-leaflets prolapse are less favorable regarding the recurrence rate of moderate or severe regurgitation, with this risk approaching 1%–2% per year –84. NeveRecently, transcatheter edge-to-edge repair emerged as an alternative to conventional surgical repair in high-risk patients unsuitable for surgery. Comparing patients treated with transcatheter and non-operated showed a significant advantage of percutaneous treatment with a prolonged higher survival rate .6.2.Yes, under few but stringent conditions.The first condition is that DMR is truly severe. If uncertainties persist, we should take advantage of multiple diagnostic techniques or refer the patient to a heart valve center for a proper assessment.The second condition is that an effective, low-risk, and durable repair can be achieved. If we cannot satisfy those requirements at our Institution, the referral of patients elsewhere represents the opportunity to improve and/or develop future internal dedicated surgical valve programs.The third condition is that the procedure is not futile in light of a reduced life expectancy due to the presence of comorbidities. Percutaneous treatment is an option for these patients.If multiple multi-center and single-center studies provided converging evidence that early surgical treatment is associated with a better long-term outcome , 76 data7.DMR is a challenging yet tremendously exciting and evolving field of medicine. Thoughtful management of MVP demands a proper and comprehensive knowledge of genetics, hemodynamics, imaging, and arrhythmias substrates.In the present article, we summarized old concepts, current orientations, and future perspectives applicable to everyday clinical practice.


Hypertension is highly prevalent in patients with obstructive sleep apnea (OSA), and fluid retention with its nighttime rostral distribution is one potential mechanism. We tested whether or not diuretics differ from amlodipine in their impact on echocardiographic parameters. Patients with moderate OSA and hypertension were randomized to receive diuretics  or amlodipine daily for 8 weeks. We compared their effects on left and right ventricular global longitudinal strain , on LV diastolic parameters, and on LV remodeling. In the 55 participants who had echocardiographic images feasible for strain analysis, all echocardiographic parameters were within normal ranges. After 8 weeks, the 24 h blood pressure (BP) reduction values were similar, while most echocardiographic metrics were kept unchanged, except for LV-GLS and LV mass. In conclusion, the use of diuretics or amlodipine had small and similar effects on echocardiographic parameters in patients with moderate OSA and hypertension, suggesting that they do not have important effects on mediating the interaction between OSA and hypertension. Obstructive sleep apnea (OSA) is characterized by recurrent complete and partial upper airway obstructive events, resulting in intermittent hypoxemia, sleep fragmentation, and daytime sleepiness. It is associated with a high prevalence of hypertension, as much as it is with heart failure, ischemic heart disease, pulmonary hypertension, arrhythmia, and stroke .It is known that there is a long installation period for these cardiovascular maladaptive mechanisms, and echocardiography permits the noninvasive evaluation of the cardiac structures and preclinical cardiac systolic and diastolic dysfunction . More reThe interaction between OSA and hypertension may lead to the development of cardiac systolic and diastolic dysfunction, but the underlying mechanisms are not well-understood. Dysautonomia and repetitive hypoxia induced by obstructive sleep apnea (OSA) can affect the interaction between oxygen supply and demand to the myocardium, leading to myocardial ischemia ,5, whichContinuous positive airway pressure (CPAP) improves blood pressure control in patients with OSA and resistant hypertension , particuIn summary, there are multiple connections between OSA, hypertension, and their cardiac dysfunctions. In this context, we tested in a randomized clinical trial the effects of a combination of chlorthalidone plus amiloride vs. amlodipine over a period of eight weeks on echocardiographic parameters of left and right ventricular function in patients with OSA and hypertension.This parallel randomized clinical trial was conducted in a university hospital and approved by the research ethics committee (GPPG: 2015-0274), which is accredited by the Office of Human Research Protection as an institutional review committee (IRB0000921). The study was performed in compliance with the amended Declaration of Helsinki. The protocol was uploaded to clinicaltrials.gov ((NCT 01896661 and NCT 02896621) and published . All parParticipants aged 40 years or older, who had undergone complete polysomnography (PSG) in the sleep laboratory, and had been diagnosed with OSA and hypertension were eligible. Hypertension was confirmed via 24 h ambulatory blood pressure monitoring (ABPM), with values of ≥130/80 mmHg, an office blood pressure (BP) of ≥140/90 mmHg or the use of antihypertensive medication. Individuals who were taking BP-lowering drugs were required to undergo a two-week washout period to determine their eligibility. The exclusion criteria comprised allergies or intolerance to the experimental drugs, secondary hypertension diagnosis, current treatment for OSA, recent diagnosis of myocardial infarction or stroke within three months, sustained arrhythmias, heart failure, low life expectancy, ongoing pregnancy, or participation in another study within the past six months.The participants were randomized to receive a combination of diuretics  or amlodipine 10 mg, administered for eight weeks as a single daily dose in the morning without dose titration. Treatment allocation was randomized and stratified by sex and OSA severity (AHI > 5–25 and 26–40 events/h) in blocks of varying sizes. Before patient enrollment, the randomization list was generated by an independent researcher (who had no contact with the participants) in Random Allocation Software 1.0 and was stored in the Research Electronic Data Capture platform . The treatment groups were concealed from the participants, doctors, and researchers until the completion of the study.Participants were evaluated at baseline with anthropometric evaluation including height, weight, and cervical circumference, laboratory tests , transthoracic echocardiography, 24 h ABPM, and total body water via bioimpedance . These measures were repeated at the end of the study.The primary endpoints were the variation after the eight weeks of left and right ventricular longitudinal strain , and Doppler LV diastolic parameters . The secondary outcomes were changes in 24 h ABPM measures, LV ejection fraction (LVEF), LV mass, relative wall thickness (RWT), left atrial volume index (LAVI), and left ventricular outflow tract velocity time integral (LVOT-VTI).Adverse events were investigated through self-reported symptoms in a semi-structured questionnaire.All participants underwent a transthoracic echocardiographic examination  with an adult sector transducer (1–5 MHz) by the same trained certified echocardiographer (JAJ), who was blinded to participants’ medication. Two-dimensional and Doppler images were acquired according to the recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging (ASE/EACI) .©, TomTec-ArenaTM 1.2 Imaging Systems, Unterschleißheim, Germany). LV-GLS was calculated from 4- and 2-chamber apical views, and RV-GLS was calculated from a 4-chamber apical view.The mean of three consecutive heart beat measurements was used in the analysis. In the parasternal longitudinal view, LV diastolic and systolic diameters, septal, and posterior wall thicknesses were measured to calculate LV mass and relative wall thickness . Final LV diastolic and systolic and left atrial systolic volumes and LV ejection fraction (LVEF) were measured in 4-chamber and 2-chamber apical views using a modified Simpson’s rule. LV mass and left atrial volume were indexed to body surface area . Early (E-wave) and late (A-wave) peak velocities were measured from spectral traces of pulsed Doppler in mitral inflow. Tissue Doppler imaging was used to obtain early septal  and lateral  mitral annulus displacement peak velocities. These parameters were used to calculate the E/A, and the mean E/e′ ratio from septal e′ and lateral e′. LVOT-VTI, a Doppler surrogate for cardiac output , was meaDuring the study, Ambulo 2400  with an adequate cuff size was employed to conduct 24 h ABPM on the non-dominant arm. Blood pressure readings were taken every 15 min while awake and every 20 min during the sleep period. Office blood pressure was measured twice using a standardized technique with an oscillometric monitor  on two separate occasions, and the average value was calculated. The extent of nighttime BP dipping was determined as the percentage difference between the mean systolic pressure during daytime and nighttime.Conventional polysomnography was assessed with a BrainNet digital instrument , which recorded the electroencephalogram , left and right electrooculogram, and submental and tibial electromyography. Airflow was measured with a nasal cannula attached to a pressure transducer . Respiratory effort was evaluated using respiratory inductance plethysmography , while pulse oximetry  was employed to monitor oxygen saturation levels. Additionally, electrocardiogram readings were taken during the night in the sleep laboratory using a single derivation, DII. In this study, obstructive apnea was characterized as a reduction in inspiratory airflow by over 90% accompanied by a minimum of 10 s of respiratory effort. Hypopnea was determined by a more than 30% reduction in respiratory flow coupled with a desaturation of over 3% or an arousal. The AHI was calculated as the number of apnea and hypopnea events per hour of sleep, with more than 5 events per hour being considered abnormal.The sample size was estimated to be 28 participants per group, based on a difference in the E/A ratio of 0.3 ± 0.4 found in a trial of an intervention with CPAP , with 80t-tests and t-tests for independent samples, with p < 0.05 being considered statistically significant. We performed additional analysis using two-way ANOVA for treatment and time and the p value for interaction was described. Intra-observer variability was determined via a duplicate assessment of LV- and RV-GLS. Intra-observer reproducibility was assessed with coefficient of variation and intraclass correlation coefficient (ICC) tests. The analyses were performed in Stata 12 .The results were presented as means and standard deviations and the frequencies as percentages. For continuous variables, variations between baseline and follow-up values in each group were compared using paired The database of patients having polysomnography between December 2014 and February 2017 was screened and most were excluded for not having OSA or refused to participate. Among those eligible, 66 were randomized—33 were randomized to the diuretics group  and 33 to the amlodipine group. One participant in the diuretics group and three in the amlodipine group were lost upon follow up, and one participant in the amlodipine group discontinued the intervention due to ankle edema but returned for the final eight-week visit. Image quality permitted the measurement of GLS in 55 participants (27 in the diuretics group and 28 in the amlodipine group), and 1 patient did not repeat the 24 h ABPM at the end of the study. The study included mostly overweight men with an average AHI of over 29 events/h. There were no significant differences between the groups in terms of their baseline demographic and clinical characteristics . There wAt the end of the eight-week intervention period, there was a significant reduction of approximately 10 mmHg in systolic and 5 mmHg in diastolic 24 h BP, with corresponding correlates in daytime and nighttime systolic and diastolic BP . These BEchocardiographic structural and functional parameters were within normal ranges and did not differ between the two groups at baseline or at the end of the follow-up period . Notablyp = 0.9). On the other hand, antihypertensive treatment had no effect on RV strain in either group. Left ventricular ejection fraction (LV-EF) also improved during the study period following the same pattern. However, parameters of diastolic function, such as lateral e′, septal e′, E/e′ ratio, E/A ratio and LAVI did not change, suggesting that LV filling pressures were not significantly affected by the allocated treatments. We also observed a reduction in left ventricular wall thicknesses, and in LVMI and RWT measurements across the study period, regardless of the allocated treatment  and intraclass correlation coefficient , as a proxy for bidimensional measurements, CV = 2.1% and ICC = 0.99 (95% CI = 0.97–0.99), as a proxy for Doppler measurements for E/e′; CV = 6.6% and ICC = 0.88 (95% CI: 0.78–0.98) for LV-GLS and CV = 7.5% and ICC = 0.65 (95% CI = 0.40–0.90)) for RV-GLS.p = 0.12).There were non-statistically-significant differences in self-reported adverse events between the two groups at the end of the study. However, it is worth noting that a slightly higher proportion of participants in the amlodipine group reported experiencing lower limb edema (48.4%) than that in the diuretic group (27.3%), although this disparity was not found to be statistically significant  and amlodipine, despite the rationale suggesting the mechanistic benefit of diuretics in OSA patients.Preliminary analysis from our data suggested that neither the administration of diuretics nor that of amlodipine had a treatment effect on the intensity of OSA suggesting that modifications in LV systolic function and LV structural parameters may be related to the blood pressure lowering of antihypertensive drugs rather than to the AHI reduction .The movement of fluid from the lower limbs to the neck area during the night altering upper airway dynamics seems to be involved in the physiopathology  and seveHypertension is likely to play a key role in LV subclinical dysfunction present in OSAS. There is robust evidence demonstrating that CPAP improves blood pressure control in patients with OSA and resistant hypertension . It is aThe effects of CPAP on LV diastolic function have shown conflicting results in the literature ,26,27,28Certain limitations should be considered when interpreting the results. The participants had a relatively low previous burden of hypertension, as indicated by their echocardiographic parameters falling within normal limits. This may have made them less susceptible to changes resulting from the intervention. The marginal significance of the treatment effect over time on echocardiographic parameters, regardless of the specific drug administered, may be secondary to the insufficient statistical power of our study.The administration of diuretics or amlodipine had small and similar effects on echocardiographic parameters in patients with moderate OSA and hypertension. The possibility that blood pressure-lowering drugs have a differential effect in patients with OSA requires further investigation in studies with larger samples.


Independent of one another, hemodynamic and non-hemodynamic left ventricular remodeling had associations in opposite directions to left ventricular systolic function and was associated directly with traditionally determined left ventricular mas indices . Non-hemodynamic cardiac remodeling parameters discriminated more effectively than traditionally determined LVMIs between patients with and without reduced ejection fraction (p < 0.04 for comparison). Left ventricular mass parameters were unrelated to impaired diastolic function in patients with CKD. Traditionally determined LVMIs are less strongly associated with impaired systolic function than non-hemodynamic remodeling parameters (p < 0.04–0.01 for comparisons) because they represent both adaptive or compensatory and non-hemodynamic cardiac remodeling.We aimed to evaluate the extent to which different left ventricular mass parameters are associated with left ventricular function in chronic kidney disease (CKD) patients. We compared the associations between traditionally determined left ventricular mass indices (LVMIs) and hemodynamic (predicted LVMIs) and non-hemodynamic remodeling parameters with left ventricular function in patients with CKD; non-hemodynamic remodeling was represented by inappropriate left ventricular mass and inappropriate excess LVMIs . Non-hemodynamic left ventricular remodeling parameters were strongly associated with impaired left ventricular systolic function ( Uremic cardiomyopathy affects up to 74% of patients with chronic kidney disease . Uremic Contemporary knowledge suggests that left ventricular hypertrophy typically develops in response to increased hemodynamic load, including that caused by enhanced pressure (afterload) and/or volume (pre-load) . In thisTraditionally determined left ventricular mass indices strongly predicts cardiovascular events independent of conventional cardiovascular risk factors and coronary artery disease ,10,11,12Very recently, and to gain further insights into the pathophysiology of heart disease among patients with primary aldosteronism, several investigators employed the novel and promising parameter-inappropriate excess left ventricular mass index ,21,22. TInappropriate left ventricular mass occurs in as much as 40 to 70% of patients with chronic kidney disease ,24, in wConceptually, hemodynamic compensatory and adaptive left ventricular remodeling, as represented by predicted left ventricular mass index, as well as non-hemodynamic left ventricular remodeling as identified by inappropriate excess left ventricular mass indices, would be expected to contribute to traditionally determined left ventricular mass indices. We, therefore, hypothesized that compared to inappropriate left ventricular mass and inappropriate excess left ventricular mass indices, traditionally determined left ventricular mass indices are less strongly associated with impaired left ventricular function and, therefore, less useful in the identification of patients with chronic kidney disease who are at increased risk of heart failure.2.This study was performed in accordance with the Helsinki Declaration, as revised in 2013. The University of Witwatersrand’s Human  Research Committee approved the protocol (protocol number: M15-08-43). Each patient provided informed written consent prior to participation. The study design was reported previously . One hunWe previously reported the applied methods were previously reported in another study ,28,29. R0 = the start of the waveform; TF =the end of the waveform; Pi = pressure points; and, n = the number of pressure points.where TCentral systolic blood pressure was measured through utilizing a high-fidelity SPC-301 micromanometer , which interfaced with a computer using SpygmoCor software, version 9.0 , as previously reported ,27 AfterEchocardiography was performed in accordance with the American Society of Echocardiography convention  by emploLeft ventricular dimensions were determined by measuring the left ventricular internal end diastolic and end systolic diameters and wall thicknesses  in the parasternal long axis view via two-dimensional directed M-mode echocardiography. The Teichholz method was used to assess left ventricular end diastolic and systolic volumes, which were indexed to body surface area (LVEDVI-BSA and LVESVI-BSA). Stroke volume was determined from the difference between left ventricular end diastolic and systolic volumes, as evaluated upon employing the Z-derived method. Cardiac output was determined as stroke volume x heart rate. Left ventricular midwall fractional shortening was assessed using the previously reported formula, i.e., [(LVIDed + 0.5 Hed)—LVIDes + 0.5 Hes)]/LVIDed + 0.5 Hed), where LVID is left ventricular internal diameter, H is wall thickness , ed is end diastole and es is end systole ,31. Left1.7 (LVMI-ht1.7). Left ventricular hypertrophy was identified as LVM-ht1.7 greater than 80 g/m1.7 for men and greater than 60 g/m1.7 for women. Stroke work (SW) was calculated as stroke volume × central systolic blood pressure x 0.014 and expressed in gram–meters/beat. Inappropriate left ventricular mass (iLVM) was determined from predicted LVM, where predicted LVM was calculated as 55.37 + (6.64 × height2.7) +  − (18.07 × sex), where male sex = 1 and female sex = 2. Inappropriate LVM was expressed as a percentage of actual LVM/predicted LVM. Increased inappropriate left ventricular mass was defined as inappropriate LVM if it recorded values above 128%. Traditionally determined left ventricular mass and inappropriate left ventricular mass could be calculated in 97 and 93 patients, respectively. Predicted LVM was then indexed to body surface area (pLVMI-BSA) and height1.7 (pLVMI-ht1.7). PLVMI-BSA and pLVMI-ht1.7 represented hemodynamic left ventricular remodeling [1.7 (ieLVMI-ht1.7), which were defined as follows: measured LVMI-BSA—pLVMI-BSA and measured LVMI-ht1.7—pLVMI-ht1.7 [Left ventricular mass (LVM) was determined using a standard formula and indexed to body surface area (LVMI-BSA) and heightmodeling ,22,23. NMI-ht1.7 ,22,23.Left ventricular relative wall thickness (RWT) was calculated as left ventricular diastolic posterior wall thickness × 2)/left ventricular end diastolic diameter. Increased relative wall thickness was determined as ≥0.45. Based on the LVMI and RWT measurements, geometric patterns were described as concentric remodeling , concentric hypertrophy (increased LVMI and increased RWT) and eccentric hypertrophy .Transmitral flow patterns were recorded at the mitral valve leaflet tips using pulsed Doppler in the apical four-chamber view. The early (E) diastolic wave was measured from the mitral inflow velocity curve. Using tissue Doppler imaging, the velocities of longitudinal myocardial tissue shortening (s’) and early diastolic mitral annulus motion (e’) were measured by placing the cursor at the septal and lateral corners of the mitral annulus. The left ventricular filling pressure index (E/e’ ratio) was calculated as mitral E/the average of septal and lateral e’. An E/e’ > 14 was considered elevated.p < 0.0001 for all) and −0.41 (4.16), 0.45 (7.74), 1.74 (6.08), 0.16 (9.95) and −1.46 (8.58), respectively.Echocardiographic measurements were made by the same observer who performed the arterial function evaluation. Intra-observer echocardiographic measurement variability was low in our setting with Pearson’s correlation coefficients and variances (mean % difference (SD)) for left ventricular end-diastolic diameter, septal wall thickness, posterior wall thickness, E and e’ of 0.92, 0.72, 0.76, 0.88 and 0.93 (Results were expressed as mean (SD), median (interquartile range) or proportions as appropriate. Non-normally distributed variables were logarithmically transformed prior to being entered into linear multivariable regression models.Data among subgroups, including non-dialysis versus dialysis patients, patients with and without traditionally determined left ventricular hypertrophy and patients with appropriate and inappropriate left ventricular mass, were compared in age-, sex- and race-adjusted models.Associations between left ventricular mass parameters and measures of diastolic and systolic function were assessed in confounder-adjusted models. Significant associations were re-evaluated via a sensitivity analysis among patients without established cardiovascular disease.To assess the contribution of hemodynamic and non-hemodynamic components of cardiac remodeling to traditionally determined left ventricular mass indices associated with left ventricular function, we performed confounder-adjusted product of coefficient mediation analysis. Mediation analysis accounts for hierarchical causal structures ,34,35,36The performance of left ventricular mass parameters in identifying patients with reduced ejection fraction was assessed using receiver operator characteristic (ROC) curve analysis. The optimal left ventricular mass parameter cut-off values required in predicting the presence of reduced ejection fraction were determined by calculating the Youden index.The data were analyzed using IBM SPSS statistical program  and Statistica 8.0 application package .The baseline recorded characteristics in all, non-dialysis and dialysis patients are given in 1.7 and eccentric hypertrophy, a larger ieLVMI-BSA and LEVDV-BSA and a smaller e’ and larger E/e’.Central pressures and left ventricular structure and function measures in all, non-dialysis and dialysis patients are shown in Baseline recorded characteristics in patients with and without traditionally determined left ventricular hypertrophy and inappropriate left ventricular mass are given in p = 0.05 and p = 0.06, respectively).Central pressures and left ventricular structure and function in patients with and without traditionally determined left ventricular hypertrophy and inappropriate left ventricular mass are shown in 1.7, a smaller predicted LVMI-BSA and larger inappropriate excess left ventricular mass indices, increased concentric remodelling, a larger LVEDV-BSA and reduced ejection fraction and midwall fractional shortening. Stroke volume, cardiac output and stroke work were also lower in patients with compared to those without inappropriate left ventricular mass but these differences did not reach significance.Compared to patients with appropriate left ventricular mass, those with inappropriate left ventricular mass had a larger LVMI-BSA and LVMI-htAs given in p = 0.05 for LVMI-BSA) or were (p = 0.04 for LVMI-ht1.7) inversely associated with ejection fraction. However, upon additional adjustment for inappropriate left ventricular mass or inappropriate excess left ventricular mass indices, traditionally determined left ventricular mass indices became directly associated with ejection fraction. In contrast, upon additional adjustment for predicted left ventricular mass indices, the inverse relationships between traditionally determined left ventricular mass indices and ejection fraction were strengthened. Additionally, left ventricular mass indices were strongly and inversely associated with midwall fractional shortening in the respective models. These phenomena are further illustrated in p = 0.03 and p = 0.04, respectively) and ejection fraction  than LVMI-BSA and LVMI-ht1.7.As applied to results obtained in univariate analysis , inapproPredicted left ventricular mass indices were directly associated with midwall fractional shortening and ejection fraction.p = 0.07 to p = 0.08) to be inversely associated with midwall fractional shortening.Inappropriate excess left ventricular mass indices were inversely related to ejection fraction and tended (p = 0.06 to p = 0.9). Hence, a stratified analysis of the left ventricular mass parameter–function relations based on dialysis status was not performed.Dialysis status did not impact any of the left ventricular mass parameter–function relations  = 0.800 (0.692–0.907)) effectively discriminated between patients with and without reduced ejection fraction, with cut-off values and corresponding sensitivities and specificities of 169, 69 and 88%, 28 g/m2 and 87 and 71%, and 20 g/m1.7 and 87 and 67%, respectively. While inappropriate excess left ventricular mass indices performed similarly to inappropriate left ventricular mass in identifying patients with reduced ejection fraction, the AUC for the inappropriate left ventricular mass–reduced ejection fraction relationship was larger than that for the LVMI-BSA–ejection fraction (p = 0.04 for comparison) and LVMI-ht1.7–ejection fraction (p = 0.04 for comparison) associations.The performances of traditionally determined left ventricular mass indices, inappropriate left ventricular mass and inappropriate excess left ventricular mass indices in identifying patients with reduced ejection fraction (<50%), as determined via ROC curve analysis, are given in This study examined and compared for the first time the potential impact of traditionally determined left ventricular mass indices, inappropriate left ventricular mass and predicted and inappropriate excess left ventricular mass indices on diastolic and systolic function in patients with chronic kidney disease. Importantly in the present context, predicted left ventricular mass indices represent hemodynamic remodeling, whereas inappropriate left ventricular mass and inappropriate excess left ventricular mass indices are markers of non-hemodynamic remodeling. Left ventricular hypertrophy and inappropriate left ventricular mass were highly prevalent in the current chronic kidney disease cohort, which is consistent with findings reported in previous studies ,5,23,24.In the present study, the most prominent novel findings in patients with chronic kidney disease were uncovered via multivariate analysis, which assessed the potential relative impact of different left ventricular mass parameters on left ventricular circumferential myocardial contractility and chamber or pump function . AssociaIn line with the above-mentioned findings, in separate models, hemodynamic and non-hemodynamic remodeling independently contributed to one another to a similar extent, albeit with opposing effects to left ventricular mass ejection fraction. Also, in mediation analysis, non-hemodynamic left ventricular remodeling accounted between 74.0 and 76.9% of the relationship between traditionally determined left ventricular mass indices and left ventricular systolic function, whereas for hemodynamic left ventricular remodeling, the respective association was between 11.2 and 17.5%.Our findings suggest that in patients with chronic kidney disease, non-hemodynamic left ventricular remodeling parameters are more strongly associated with impaired left ventricular systolic function than traditionally determined left ventricular mass indices, because the latter approach represents both compensatory and adaptive hemodynamic left ventricular remodeling that aims to preserve wall stress in the face of increased pressure (concentric hypertrophy) and maintain a large stroke volume in the presence of increased volume load (eccentric hypertrophy), as well as cause adverse and maladaptive non-hemodynamic left ventricular remodeling . Indeed,Systolic heart failure in hypertensive patients was previously found to be associated with reduced mysial collagen deposits and increased perivascular- and scar-related collagen deposits. Reduced mysial collagen can adversely impact systolic function through decreased support, geometric alignment and coordination of adjacent cardiomyocyte fascicle contraction; impaired synchrony and synergy of sarcomeres during contraction; and sliding displacement of cardiomyocytes . WhetherThis study revealed that e’ and E/e’ were similar in CKD patients with and without traditionally determined left ventricular hypertrophy and inappropriate left ventricular mass in patients with chronic kidney disease. Also, in both univariate and confounder-adjusted multivariable regression models, traditionally determined left ventricular mass indices, as well as inappropriate left ventricular mass and inappropriate excess left ventricular mass indices, were not associated with diastolic function. Left ventricular hypertrophy is mostly thought to contribute to diastolic dysfunction in patients with essential hypertension  and CKD In the current investigation, predicted left ventricular mass indices, stroke volume, cardiac output and stroke work were each increased in patients with compared to without traditionally determined left ventricular hypertrophy, but were not increased in patients with compared to without inappropriate left ventricular hypertrophy. Also, in line with previous reports in patients with hypertension , inapproThe current study has limitations. Firstly, given its cross-sectional design, we cannot determine the direction of causality. Secondly, while we did not find differences in left ventricular mass parameter–left ventricular function relationships among non-dialysis and dialysis patients, inclusion of larger numbers of patients may reveal an impact of dialysis status on the respective associations. This possibility requires further investigation. Thirdly, systolic blood pressure was measured in the clinic. Blood pressure tends to fluctuate markedly over time in patients with chronic kidney disease . The useOur findings show the need for future larger and longitudinal studies to further elucidate the pathophysiological mechanisms that account for the impact of hemodynamic and non-hemodynamic remodeling on cardiac function in patients with chronic kidney disease.Non-hemodynamic left ventricular remodeling is strongly associated with impaired left ventricular systolic function, whereas hemodynamic left ventricular remodeling relates strongly but directly to left ventricular systolic function. Independent of one another, hemodynamic and non-hemodynamic left ventricular remodeling associate with left ventricular systolic function (but in opposite directions) and directly associate with traditionally determined left ventricular mas indices. Non-hemodynamic remodeling contributes more than hemodynamic remodeling to traditionally determined left ventricular mass. Consequently, traditionally determined left ventricular mass indices are far less strongly associated with impaired left ventricular systolic function than inappropriate left ventricular mass and inappropriate excess left ventricular mass indices. Non-hemodynamic, but not hemodynamic, left ventricular mass parameters discriminates effectively between patients with and without reduced ejection fraction. Left ventricular mass parameters are not associated with impaired diastolic function in patients with chronic kidney disease. The most important practical implication in this study is that compared to traditionally determined left ventricular mass indices, inappropriate left ventricular mass and inappropriate excess left ventricular mass indices are substantially more useful and, therefore, preferable in identifying chronic kidney disease patients with systolic dysfunction, who are known to be at higher risk of risk of heart failure with reduced ejection fraction.


Conduction system pacing (CSP) has been emerging over the last decade as a pacing option instead of conventional right ventricular (RV) pacing and biventricular (BiV) pacing. Numerous case reports, some observational studies and a few randomized control trials have looked at optimum pacing strategies for heart failure (HF) with left bundle branch block (LBBB) or cases where left ventricular (LV) dysfunction is anticipated due to chronic RV pacing (RVP). Evolution of pacing strategies from standard RVP to septal RVP, BiV pacing and now CSP have shown improving hemodynamic responses and possible ease of implantation of CSP systems. In this review article, we review the literature on the evolution of CSP and common scenarios where it might be beneficial. The cardiac conduction system comprises specialized cells with properties of automaticity and conduction. The sinoatrial (SA) node and the atrioventricular (AV) node can function as pacemakers with the ability of automaticity. The Bundle of His, approximately 18 mm long in an adult heart, traverses the right fibrous trigone commonly dividing into two specialized bundle branches . These are encapsulated by a fibrous sheath that separates the specialized myocytes from the myocardium thus allowing rapid electrical conduction. At the distal branches of these bundles, there is absence of this fibrous sheath, allowing communication with the local ventricular myocardium resulting in myocardial contraction  (1). TheLBBB cause interventricular dyssynchrony with RV systole earlier than LV systole. It also contributes to intraventricular dyssynchrony, which is a result of myocyte-to-myocyte propagation of signal from RV to LV through the septum, with the earliest breakthrough of signals being the LV septum and the latest being the inferior-basal LV wall. This mechanical disparity results in a pre-systolic stretch of the late activated areas, which by way of Frank-Starling law results in an enhanced systolic, albeit late, contraction. As a result, systolic stress, strain, and myocardial oxygen consumption is increased in late activated regions and reduced in early activated regions, with subsequent loss of pumping efficiency –4.Disruption of the conduction system can have varying detrimental effects. Early landmark data, such as the Framingham study, showed that new LBBB was associated with underlying coronary artery disease, cardiomyopathies, infiltrative diseases and heart failure . IncidenLandmark clinical trials had shown that resynchronization with Biventricular Pacing—Cardiac Resynchronization therapy (BiV-CRT) improved quality of life, reduced LV remodeling, and reduced cardiovascular outcomes such as hospitalization and mortality in patients with impaired LV function in the setting of LBBB –12. CorrThere is minimal evidence supported by case reports to suggest that correcting the LBBB in preserved LV function has any long-term benefit . More stPatients with symptomatic SA node disease and AV block will require pacemakers. The pacemakers can be RV-only, dual-chamber pacemakers, CRT, endocardial LV lead, HIS Bundle pacing (HBP) or LBBAP . AdvanciRight ventricular pacing (RVP) has saved the lives of a substantial number of people, especially those with sick sinus syndrome (SSS) and AV block such as complete heart block (CHB). However, chronic RVP has resulted in LV dysfunction in some patients.The placement of the leads at the RV has deleterious effects on the normal functioning of the heart with the weakening of heart muscle, heart failure and risk of arrhythmia. Pacing-induced cardiomyopathy (PICM) from chronic high burden RVP has varied in definitions across studies, with several different thresholds for drop in LVEF identified. Most widely used definition is drop in LVEF to less than 40%–50%, with an absolute drop in LVEF of at least 5%–10%, with 10%–20% of patients with normal LVEF speculated to develop PICM from chronic high burden RVP –19. PermConduction system pacing (CSP) requires engaging the conduction system at either the level of the His bundle (HBP) or the left bundle branch (LBBAP) resulting in myocardial capture that is considered physiological. Physiological pacing through CSP has been evolving to avoid the unfavourable effects of RV pacing resulting in ventricular dyssynchrony –24.HBP is considered the most physiological as it captures the proximal origin of the ventricular conduction system beyond the AV node, and proximal BBB can be corrected at its level due to the longitudinal dissociation theory , 26. ThiDespite HBP being the optimal pacing site for a physiological response, it has its limitations. The technique of HBP requires precision skills in targeting a small zone and is found to be challenging in patients with distorted anatomy due to dilated hearts, resulting in high fluoroscopic radiation exposure and a long duration of procedures. Oversensing the atrial and undersensing the ventricular signals is a frequent concern due to the anatomical location of HBP. The success rate of achieving HBP with predefined parameters varies between 76% and 96% depending on the operator's experience and the level of conduction system disease . There iLBBAP technique was first described by Huang et al. in 2017 by capturing the LBB area deep into the RV septum in a patient with heart failure and LBBB , 39. DepLBBAP has shown to be safe and effective in LBBB patients with LV impairment to maintain or improve cardiac function compared to RV pacing and BiV-CRT pacing, while taking a shorter time and less radiation exposure to the patient than HBP . Early sLBBAP represents a natural evolution of conduction system pacing to overcome the challenges posed by the current limitations of HBP . There aFor instances where adequate narrowing of the QRS cannot be achieved by HBP due to distal conduction tissue disease, His optimized CRT (HOT-CRT) was considered an alternative for narrowing QRS by fusion of HBP and LV pacing via the coronary sinus . SimilarCurrent recommendations for CSP (HBP or LBBAP) from the 2023 HRS/APHR/LAHRS guidelines include patients with indications for pacemaker therapy with anticipated ventricular pacing ≥40% and an LVEF of 36%–50% (class IIa) or LVEF >50% (class IIb). CSP maybe considered if less than 40% pacing is anticipated, with LVEF of 36%–50%, with or without a LBBB (class IIb), whereas only LBBAP maybe considered if LVEF is >50% (class IIb). CSP maybe also considered in HF patients with LBBB, LVEF 36%–50%, QRSd ≥150 ms and NYHA class II-IV (class IIb), or if effective CRT cannot be achieved with BiV pacing and LVEF ≤35% (class IIa). In patients with non-LBBB, LVEF ≤35%, QRSd 120–149 and NYHA class III–IV, CSP could be considered (class IIb) .BiV pacing (BVP) was developed in the early 2000s by pacing both ventricles resulting in fusion and correcting BBB in the management of heart failure . Conventmax) of the LV, is one of the oldest measures of LV global contractility and is a good index of ventricular performance. Shortening of an inappropriately long AV delay by CRT results in an earlier pressure development in the LV due to pre-excited pacing, increasing the pulse pressure and LV dP/dTmax  and broad QRS and has shown to have promising results as supported by a recent meta-analysis . There hP < 0.001), improved LVEF , reduced LV end-diastolic dimension , improved NYHA class , and higher echocardiographic and clinical response rate (P < 0.001). Furthermore, LBBP demonstrated higher clinical and echocardiographic response, especially higher super-response (≥20% absolute increase or LVEF ≥50%) compared to BVP-aCRT  compares CSP to BiV-CRT in 130 patients with indications for CRT, and Left vs. Left (NCT05650658) comparing both pacing strategies in 2,136 patients with LVEF <50%, RAFT-Preserved (NCT04582578) compares CSP to BiV-CRT in HF with preserved ejection fraction, RAFT P&A (NCT05428787) compares LBBAP to BiV-CRT in patients with AF underdoing a pace and ablate strategy, CSP-SYNC (NCT05155865), HOT-CRT (NCT04561778), PHYSPAVB (NCT05214365) compares CSP versus conventional RV pacing, LEAP (NCT04595487) compares CSP to RV pacing, LEAP-Block (NCT04730921) compares LBBAP to RV pacing in patients with AV block, HIS-PrEF (NCT04529577) compares RV pacing to HBP in HFrEF, HIS-alt_2 (NCT04409119) compares CSP to BiV-CRT in HFrEF with LBBB, LBBAP-AFHF (NCT05549544) compares LBBAP with BiV pacing in patients requiring an AV node ablation in LVEF <50%, LEFT-BUNDLE-CRT (NCT05434962) compares LBBAP to BiV-CRT in HFrEF. Some of these studies are reviewing the clinical effectiveness of CSP to current conventional and gold standards such as BiV-CRT with outcomes targeting electrical (QRS), function (LVEF) and biochemical changes (NT-proBNP). Other studies are looking at mechanisms of clinical response, and myocardial activation sequence using CSP compared to BiV.The rapid acceptance and evolution of CSP along with its safety has led to rapid growth of research in multiple facets being explored. Current randomized recruiting studies on CSP listed on Conduction tissue pacing in HIS Bundle pacing and LBBAP is feasible, safe, and quicker, with results comparable to cardiac resynchronization therapy. Extensive studies are required to directly compare the long-term clinical effectiveness of conduction system pacing against CRT.