Kandlakunta, Sriharsha

Background: Hypertension is a major contributor to global cardiovascular morbidity and mortality. Despite a wide range of pharmacologic treatments, many patients continue to have uncontrolled blood pressure. Recent research highlights the gut microbiota as a modifiable factor in blood pressure regulation through mechanisms involving systemic inflammation, microbial metabolites such as short-chain fatty acids, and angiotensin-converting enzyme modulation. Probiotic and prebiotic supplementation has gained interest as an adjunct strategy, yet existing reviews are limited in scope and often lack robust subgroup analysis. Objective: To systematically evaluate the effect of probiotic and prebiotic supplementation on blood pressure in adults with hypertension or elevated blood pressure, with an emphasis on gut microbiota modulation. Methods: We conducted a systematic search of PubMed, Scopus, Cochrane CENTRAL, and ScienceDirect for articles published from May 1, 2015, to April 30, 2025. ClinicalTrials.gov and PROSPERO were also searched. Eligible studies were randomized controlled trials in English involving adults 19-44 years with hypertension or pre-hypertension, comparing probiotic or prebiotic interventions with placebo, no treatment, or standard care. The primary outcome were changes in systolic and diastolic blood pressure; secondary outcomes included gut microbiota composition, inflammatory markers, endothelial function, and adverse effects. Two independent reviewers screened studies and assessed quality using the Cochrane Risk of Bias Tool 2.0. Results: Of 601 records screened, 23 trials met inclusion criteria. Most studies showed modest reductions in systolic and diastolic blood pressure with probiotic or prebiotic use. Mechanistic insights included improved gut barrier integrity, reduced inflammation, and increased beneficial metabolites. Subgroup analyses suggested efficacy varied by strain type, dosage, duration, and delivery method. Secondary outcomes showed improvements in lipid profiles, insulin resistance, and abundance of Bifidobacterium. Conclusion: Modulation of gut microbiota shows potential as an adjunct approach in managing hypertension.. While short-term benefits are observed, variability across studies limits generalizability. Larger trials with standardized methods are needed to confirm long-term clinical relevance. Keywords: Hypertension, Blood Pressure, Gut Microbiota, Probiotics, Prebiotics, Randomized Controlled Trials, Systematic Review

Introduction: The relative diagnostic and prognostic performance of left ventricular global longitudinal strain (LVGLS) as compared to LV ejection fraction (LVEF), and the role of LVGLS for detecting early stages of LV systolic dysfunction in adults with repaired coarctation of aorta (COA) is unknown. Objective: The purpose of this study was to address these knowledge gaps. Methods: Retrospective cohort study of adults with repaired COA that underwent transthoracic echocardiogram (2003-2020). LV systolic function was assessed using LVEF (derived from volumetric analysis) and LVGLS (derived from speckle-tracking echocardiography). Results: Of the 795 patients (age 36±14 years), mean LVEF and LVGLS were 62±11%, and 21±4%, respectively. The prevalence of LV systolic dysfunction was higher when assessed using LVGLS as compared to LVEF (20% versus 6%, p<0.001). Of 795 patients, 94 (12%) patients died, of which 75 (9%) died from cardiovascular causes. LVGLS provided more robust prognostic power in predicting all-cause mortality as compared to LVEF as evidenced by a higher C -statistic (0.743, 95%CI 0.730-0.755 versus 0.782, 95% CI 0.771-0.792, p<0.001). Furthermore, patients with normal LVEF in the setting of reduced LVGLS had a higher risk of all-cause mortality (as compared to patients with normal LVGLS and LVEF) and were at risk for temporal decline in LVEF during follow-up. Conclusions: These findings suggest that the use of LVGLS for risk stratification can help identify high-risk patients, and provide opportunities for interventions, which would, in turn, improve clinical outcomes. Further studies are required to empirically test these postulates.

Introduction: Right ventricular (RV) systolic dysfunction and pulmonary hypertension is present in 20% of adults with repaired coarctation of aorta (COA). However, the prognostic value of RV to pulmonary artery (RV-PA) coupling in this population is unknown. Objective: The purpose of this study was to assess the relationship between RV-PA coupling and clinical outcomes (heart failure hospitalization and all-cause mortality) in this population. Methods: Retrospective cohort study of adults with repaired COA and normal RV systolic function defined as RV-free wall strain ≥-24%. RV-PA coupling was assessed using tricuspid annular plane systolic excursion/ RV systolic pressure (TAPSE/RVSP) ratio. Results: Of 509 patients (median age 32 [20-45] years; men 290 [57%]), the average TAPSE and RVSP were 22±5 mm and 33±9 mmHg, respectively, and TAPSE/RVSP ratio was 0.78 (0.56-0.96) mm/mmHg. Of 509 patients, 51 (10%) died and 43 (8%) were hospitalized for heart failure. TAPSE/RVSP was associated with all-cause mortality (hazard ratio 0.82, 95% confidence interval 0.78-0.86, per 0.1 mm/mmHg), and heart failure hospitalization (hazard ratio 0.86, 95% confidence interval 0.79-0.83, per 0.1 mm/mmHg) after adjustment for anatomic lesions, cardiovascular interventions, comorbidities, and echocardiographic indices. The inclusion of TAPSE/RVSP ratio in the risk models improved the prognostic power of the models to predict all-cause mortality (C-statistics difference 0.046, p<0.001), and heart failure hospitalization (C-statistics difference 0.031, p=0.007). Conclusions: TAPSE/RVSP ratio was associated with outcomes in COA patients with normal RV systolic function, suggesting that abnormal RV-PA coupling may be present prior to the onset of overt RV systolic function in this population.

Introduction: Adults with repaired tetralogy of Fallot (TOF) have right atrial (RA) remodeling and dysfunction, and RA function can be measured using speckle-tracking echocardiography. There is limited data about the role of RA strain imaging in risk stratification in this population. Hypothesis: We hypothesized that RA reservoir strain could identify TOF patients at risk of developing atrial arrhythmia. We assessed the relationship between RA reservoir strain and atrial arrhythmias in adults with repaired TOF to test this hypothesis. Methods: Retrospective cohort study of adults with repaired TOF, and no prior history of atrial arrhythmias. Atrial arrhythmia was defined as atrial fibrillation, atrial flutter/atrial tachycardia, and categorized as new onset versus recurrent atrial arrhythmias. Results: We identified 426 patients (age 33±12 years; males 208 (49%)) that met the inclusion criteria. The mean RA reservoir, conduit, and booster strains were 34±11%, 20±9%, and 15±12%, respectively. Of 426 patients, 73 (17%) developed new-onset atrial arrhythmias (atrial flutter/tachycardia n=42; atrial fibrillation n=31); annual incidence 1.9%. RA reservoir strain was associated with new-onset atrial arrhythmias (adjusted HR 0.95, 95% CI 0.93-0.97) after multivariable adjustment. Of 73 patients with new-onset atrial arrhythmia, 41 (56%) had recurrent atrial arrhythmia (atrial flutter/tachycardia n=18; atrial fibrillation n=23); annual incidence 11.2%. Similarly, RA reservoir strain was associated with recurrent atrial arrhythmias (adjusted HR 0.92, 95% CI 0.88-0.96) after multivariable adjustment. Conclusions: RA strain indices can identify patients at risk for atrial arrhythmias, and this can, in turn, be used to guide the type/intensity of therapy in such patients.