Impact of Left Atrial Pressure on Outcomes After Mitral Transcatheter Edge-to-Edge Repair.

Background: Increased left atrial pressure (LAP) has been associated with adverse outcomes after mitral transcatheter edge-to-edge repair (M-TEER). We sought to evaluate outcomes based on differences in post-procedural LAP measured after final clip deployment. Methods: We included consecutive patients who underwent M-TEER at our institution between 2014-2022 with LAP monitoring. Patients were stratified into 3 groups according to tertiles of post-TEER mean LAP. Outcomes were assessed using Kaplan-Meier analysis and Cox proportional hazard models. Results: We included 273 patients (mean age 76.8±10.8 years, 42.5% women, 78.4% Caucasian). The mean post-TEER LAP was 8.7±1.7 mmHg in tertile 1 (N=85), 14.4±1.6 mmHg in tertile 2 (N=95), and 21.9±3.8 mmHg in tertile 3 (N=93). In comparison with tertile 1, both tertiles 2 and 3 were associated with increased risk of all-cause mortality or heart failure hospitalization at 2 years (adjHR 2.27, 95% CI 1.25-4.12; and adjHR 3.00, 95% CI 1.59-5.64 respectively). Among patients with primary MR, higher LAP was associated with increased risk of 2-year all-cause mortality or heart failure hospitalization [tertile 2 vs. 1: adjHR 3.00, 95% CI 1.37-6.56; and tertile 3 vs. 1: adjHR 5.52, 95% CI 2.04-14.95). However, in patients with secondary MR, neither being in tertile 2 (adjHR 1.53; 95% CI 0.55-4.24), nor tertile 3 (adjHR 2.18; 95% CI 0.82-5.77) were associated with the composite outcome compared with tertile 1. Any degree of LAP reduction following M-TEER was associated with lower mortality or heart failure hospitalization compared with no LAP reduction (adjHR 0.59; 95% CI 0.39-0.88). Conclusions: Elevated LAP after M-TEER was associated with increased 2-year risk of mortality or heart failure hospitalization. Exploration of reasons for elevated LAP after M-TEER, and ways to lower it warrant further investigation.

Prognostic Value of Right Ventricular Afterload in Patients Undergoing Mitral Transcatheter Edge-to-Edge Repair.

BACKGROUND: Pulmonary hypertension (PH) and secondary mitral regurgitation (MR) are associated with adverse outcomes after mitral transcatheter edge-to-edge repair. We aim to study the prognostic value of invasively measured right ventricular afterload in patients undergoing mitral transcatheter edge-to-edge repair. METHODS AND RESULTS: We identified patients who underwent right heart catheterization ≤1 month before transcatheter edge-to-edge repair. The end points were all-cause mortality and a composite of mortality and heart failure hospitalization at 2 years. Using the receiver operating characteristic curve-derived threshold of 0.6 for pulmonary effective arterial elastance ([Ea], pulmonary artery systolic pressure/stroke volume), patients were stratified into 3 profiles based on PH severity (low elastance [HE]: Ea <0.6/mean pulmonary artery pressure (mPAP)) <35; High Elastance with No/Mild PH (HE-): Ea ≥0.6/mPAP <35; and HE with Moderate/Severe PH (HE+): Ea ≥0.6/mPAP ≥35) and MR pathogenesis (Primary MR [PMR])/low elastance, PMR/HE, and secondary MR). The association between this classification and clinical outcomes was examined using Cox regression. Among 114 patients included, 50.9% had PMR. Mean±SD age was 74.7±10.6 years. Patients with Ea ≥0.6 were more likely to have diabetes, atrial fibrillation, New York Heart Association III/IV status, and secondary MR (all P<0.05). Overall, 2-year cumulative survival was 71.1% and was lower in patients with secondary MR and mPAP ≥35. Compared with patients with low elastance, cumulative 2-year event-free survival was significantly lower in HE- and HE+ patients (85.5% versus 50.4% versus 41.0%, respectively, P=0.001). Also, cumulative 2-year event-free survival was significantly higher in patients with PMR/low elastance when compared with PMR/HE and patients with secondary mitral regurgitation (85.5% versus 55.5% versus 46.1%, respectively, P=0.005). CONCLUSIONS: Assessment of the preprocedural cardiopulmonary profile based on mPAP, MR pathogenesis, and Ea guides patient selection by identifying hemodynamic features that indicate likely benefit from mitral-transcatheter edge-to-edge repair in PH or lack thereof.

Echocardiographic Profiling Predicts Clinical Outcomes After Mitral Transcatheter Edge-to-Edge Repair.

BACKGROUND: Prior studies investigating the impact of residual mitral regurgitation (MR), tricuspid regurgitation (TR), and elevated predischarge transmitral mean pressure gradient (TMPG) on outcomes after mitral transcatheter edge-to-edge repair (TEER) have assessed each parameter in isolation. We sought to examine the prognostic value of combining predischarge MR, TR, and TMPG to study long-term outcomes after TEER. METHODS AND RESULTS: We reviewed the records of 291 patients who underwent successful mitral TEER at our institution between March 2014 and June 2022. Using well-established outcomes-related cutoffs for predischarge MR (≥moderate), TR (≥moderate), and TMPG (≥5 mm Hg), 3 echo profiles were developed based on the number of risk factors present (optimal: 0 risk factors, mixed: 1 risk factor, poor: ≥2 risk factors). Discrimination of the profiles for predicting the primary composite end point of all-cause mortality and heart failure hospitalization at 2 years was examined using Cox regression. Overall, mean age was 76.7±10.6 years, 43.3% were women, and 53% had primary MR. Two-year event-free survival was 61%. Predischarge TR≥moderate, MR≥moderate, and TMPG≥5 mm Hg were risk factors associated with the primary end point. Compared with the optimal profile, there was an incremental risk in 2-year event-rate with each worsening profile (optimal as reference; mixed profile: hazard ratio (HR), 2.87 [95% CI, 1.71-5.17], P<0.001; poor profile: HR, 3.76 [95% CI, 1.84-6.53], P<0.001). Echocardiographic profile was statistically associated with the 2-year mortality end point (optimal as reference; mixed profile: HR, 3.55 [95% CI, 1.81-5.96], P<0.001; poor profile: HR, 3.39 [95% CI, 2.56-7.33], P=0.02). CONCLUSIONS: The echocardiographic profile integrating predischarge TR, MR, and TMPG presents a novel prognostic stratification tool for patients undergoing mitral TEER.

Prediction of breath-holding spells based on electrocardiographic parameters using machine-learning model.

BACKGROUND: Breath-holding spells (BHS) are common in infancy and early childhood and may appear like seizures. Factors such as autonomic dysfunction and iron deficiency anemia are thought to contribute to the incidence of BHS. In this study, electrocardiographic (ECG) parameters of patients with BHS were compared to those of healthy, normal children. Logistic regression and machine-learning (ML) models were then created to predict these spells based on ECG characteristics. METHODS: In this case-control study, 52 BHS children have included as the case and 150 healthy children as the control group. ECG was taken from all children along with clinical examinations. Multivariate logistic regression model was used to predict BHS occurrence based on ECG parameters. ML model was trained and validated using the Gradient-Boosting algorithm, in the R programming language. RESULTS: In BHS and control groups, the average age was 11.90 ± 6.63 and 11.33 ± 6.17 months, respectively (p = .58). Mean heart rate, PR interval, and QRS interval on ECGs did not differ significantly between the two groups. BHS patients had significantly higher QTc, QTd, TpTe, and TpTe/QT (all p-values < .001). Evaluation of the ML model for prediction of BHS, fitting on the testing data showed AUC, specificity, and sensitivity of 0.94, 0.90, and 0.94 respectively. CONCLUSION: There are repolarization changes in patients with BHS, as the QTc, QTd, TpTe, and TpTe/QT ratio were significantly higher in these patients, which might be noticeable for future arrhythmia occurrence. In this regard, we developed a successful ML model to predict the possibility of BHS in suspected subjects.

Right ventricle toxicity in cancer treatment: a focused review on cardiac imaging.

Background: The right ventricle (RV) remains the 'forgotten chamber' in the clinical assessment of cancer therapy-related cardiac dysfunction (CTRCD). Aim: We aimed to review the role that various cardiac imaging modalities play in RV assessment as part of the integrative management of patients undergoing cancer therapy. Discussion: RV assessment remains challenging by traditional 2D echocardiography. In this review we discuss other parameters such as right atrial strain, and other echocardiographic modalities such as 3D and stress echocardiography. We also elaborate on the specific role that cardiac magnetic resonance imaging and equilibrium radionuclide angiocardiography can play in assessing the RV. Conclusion: Biventricular function should be monitored following chemotherapy for early detection of subclinical CTRCD and possible solitary RV changes.

Cancer is among the most common health concerns worldwide. In addition to cancer's effects itself on the body, chemotherapy agents and medication, drug treatments that use powerful chemicals to kill cancer cells, are putting further strain on individuals' bodies impairing their quality of life. Chemotherapy agents are a major risk factor for cardiac injuries by their cardiotoxic effects (the damage they cause to the heart). Previous studies have tried to find the earliest way of noticing cardiac changes in patients who are receiving special chemotherapy drugs. Most of the studies and definitions for this cardiotoxic event are limited to the assessment of left ventricles, one of the chambers of the heart that is involved in providing oxygenated blood to the body. However, there is some evidence that suggests the evaluation of the right ventricle, another chamber of the heart that pumps blood low in oxygen to the lungs, for faster notice. Having this insight can open new targets for cancer therapy-related cardiac dysfunction (CTRCD) prevention and therapy.

Time-varying effect of postoperative cholesterol profile on long-term outcomes of isolated coronary artery bypass graft surgery.

BACKGROUND: Controlling cholesterol levels is one of the primary goals of preventing atherosclerotic plaque progression in patients undergoing coronary artery bypass graft (CABG) surgery. This study aimed to investigate the impact of serum cholesterol profile at multiple time points following isolated CABG surgery on long-term patient outcomes. METHOD: This retrospective cohort study was conducted on the admission and follow-up data of isolated CABG patients from the Tehran Heart Center registry between 2009 and 2016. The association of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and their ratio as an atherogenic index with major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality were evaluated using time-varying survival analysis methods. RESULT: A total of 18657 patients were included in this analysis. After adjusting for known confounding factors, no significant difference in all-cause mortality and MACCE was observed at different LDL levels. The incidence of acute coronary syndrome (ACS) in patients with LDL > 100 mg/dl and LDL < 50 mg/dl was significantly higher than in the control group (P-value = 0.004 and 0.04, respectively). The incidence of cerebrovascular accidents (CVA) at LDL > 100 mg/dl was also significantly higher compared to the control group (P -value = 0.033). Lower HDL levels were significantly associated with a higher MACCE (P -value < 0.001), all-cause mortality (P -value < 0.001), ACS (P -value = 0.00), and CVA (P -value = 0.014). The atherogenic index was also directly related to MACCE and all its components (all P-values < 0.001). CONCLUSION: LDL/HDL ratio is suggested as a better marker for secondary prevention goals compared to LDL alone in patients undergoing CABG surgery.

Prognostic Value of Patient-Reported Outcomes in Predicting Long-Term Mortality After Transcatheter Aortic Valve Replacement.

Background Patient-reported outcome measures have been shown to have important prognostic value after various cardiac interventions. We assessed the association between the change in Kansas City Cardiomyopathy Questionnaire 12 (KCCQ-12) score after transcatheter aortic valve replacement and mortality. Methods and Results We included patients who underwent transcatheter aortic valve replacement at Mayo Clinic between February 2012 to June 2022 and who completed a KCCQ-12 before and 30 to 45 days after the procedure. Patients were categorized into 3 groups: those who experienced significant (>+19 points; group 1), modest (1-19 points; group 2), and no (≤0 points; group 3) improvement. A total of 1124 patients were included: 60.8% men; 97.6% White. Mean age was 79.4±8.3 years, baseline KCCQ-12 score was 53.9±24.5, and median Society of Thoracic Surgeons score was 4.9% (interquartile range, 3.1-8.0). At 45 days, the mean change in KCCQ-12 score was 19±24 points; 46.3% (n=520) of patients had a significant improvement in their KCCQ-12 score, while 33.4% (n=375) and 20.4% (n=229) had modest and no improvement, respectively. Median survival was higher in group 1 (5.7±0.2 years) compared with groups 2 and 3 (5.1±0.3 and 4.1±0.4 years, respectively; P<0.001). Compared with patients in group 1, those in groups 2 and 3 had higher long-term risk-adjusted mortality (adjusted hazard ratios, 1.54 [95% CI, 1.20-1.96], and 2.30 [95% CI, 1.74-3.04], respectively). Conclusions Patients who experience modest or no improvement in KCCQ-12 score after transcatheter aortic valve replacement have substantially higher long-term mortality. Delta KCCQ-12 is a cost-effective, efficient tool that can identify patients at increased risk of death at long-term follow-up post-transcatheter aortic valve replacement.

Utilization and outcomes of protamine after percutaneous left atrial appendage occlusion.

OBJECTIVES: The aim of this study was to describe the use pattern and outcomes of protamine administration for heparin reversal among sites performing percutaneous left atrial appendage occlusion (LAAO). METHODS: We identified 45,135 patients who underwent LAAO at 243 hospitals participating in Vizient® Clinical Database between January 1, 2016 and December 31, 2021. Patients were stratified according to protamine administration after the procedure. Outcomes of interest included vascular complications, major bleeding, ischemic events, and same-day discharge. RESULTS: A total of 40,278 patients were included in the propensity-matched comparison, of whom 50% received protamine after the LAAO procedure. The use of protamine varied across hospitals, with 88 hospitals (36.2%) using protamine in >75% of cases and 32 hospitals (13.1%) not using protamine at all. Major bleeding occurred less frequently in the protamine group compared with the control group (2.4% vs. 2.8%, p = 0.03). Major vascular complications and pericardial tamponade were rare but slightly higher in the protamine group (0.8% vs. 0.6%, p = 0.04) and (1.0% vs. 0.8%, p = 0.01), respectively. There were no differences in the rates of ischemic or hemorrhagic stroke, all-cause mortality, or the rate of any major adverse event between the two groups. Same-day discharge was more frequent in the protamine group (12.3% vs 9.4%, p ≤ 0.001). CONCLUSIONS: Protamine is used in approximately 50% of LAAO procedures and is associated with lower bleeding events and higher rates of same-day discharge. The higher vascular complication and tamponade is likely due to its ad-hoc use as a reversal agent in these patients.

Predictors of hemodynamic response to mitral transcatheter edge-to-edge repair.

BACKGROUND: Improvement in left atrial pressure (LAP) during transcatheter edge-to-edge repair (TEER) is associated with improved outcomes. We sought to investigate the predictors of optimal hemodynamic response to TEER. METHODS: We identified patients who underwent TEER at Mayo Clinic between May 2014 and February 2022. Patients with missing LAP data, an aborted procedure, and those undergoing a concomitant tricuspid TEER were excluded. We performed a logistic regression analysis to identify predictors of optimal hemodynamic response to TEER (defined as LAP ≤ 15 mmHg). RESULTS: A total of 473 patients were included (Mean age 78.5 ± 9.4 years, 67.2% males). Overall, 195 (41.2%) achieved an optimal hemodynamic response after TEER. Patients who did not achieve an optimal response had higher baseline LAP (20.0 [17-25] vs. 15.0 [12-18] mmHg, p < 0.001), higher prevalence of AF (68.3% vs. 55.9%, p = 0.006), functional MR (47.5% vs. 35.9%, p = 0.009), annular calcification (41% vs. 29.2%, p = 0.02), lower left ventricular EF (55% vs. 58%, p = 0.02), and more frequent postprocedural severe MR (11.9% vs. 5.1%, p = 0.02) and elevated mitral gradient >5 mmHg (30.6% vs. 14.4%, p < 0.001). In the multivariate logistic regression analysis, AF (OR = 0.58; 95% CI = 0.35-0.96; p = 0.03), baseline LAP (OR = 0.80; 95% CI = 0.75-0.84; p < 0.001) and postprocedural mitral gradient <5 mmHg (OR = 0.35; 95% CI = 0.19-0.65; p < 0.001), were independent predictors of achieving an optimal hemodynamic response. In the multivariate model, residual MR was not independently associated with optimal hemodynamic response. CONCLUSIONS: Optimal hemodynamic response is achieved in 4 in 10 patients undergoing TEER. AF, higher baseline LAP, and higher postprocedural mitral gradient were negative predictors of optimal hemodynamic response after TEER.

Hematuria during the right heart catheterization procedure: Renal perforation as a very rare complication.

The occurrence of hematuria during a right heart catheterization can be a sign of renal perforation, a rare but life-threatening complication that could be developed due to the misdirection of wire into the abdominopelvic venous plexus. We showed this complication could be managed with venoplasty of the common iliac vein.

Emerging role of mesenchymal stem/stromal cells (MSCs) and MSCs-derived exosomes in bone- and joint-associated musculoskeletal disorders: a new frontier.

Exosomes are membranous vesicles with a 30 to 150 nm diameter secreted by mesenchymal stem/stromal cells (MSCs) and other cells, such as immune cells and cancer cells. Exosomes convey proteins, bioactive lipids, and genetic components to recipient cells, such as microRNAs (miRNAs). Consequently, they have been implicated in regulating intercellular communication mediators under physiological and pathological circumstances. Exosomes therapy as a cell-free approach bypasses many concerns regarding the therapeutic application of stem/stromal cells, including undesirable proliferation, heterogeneity, and immunogenic effects. Indeed, exosomes have become a promising strategy to treat human diseases, particularly bone- and joint-associated musculoskeletal disorders, because of their characteristics, such as potentiated stability in circulation, biocompatibility, low immunogenicity, and toxicity. In this light, a diversity of studies have indicated that inhibiting inflammation, inducing angiogenesis, provoking osteoblast and chondrocyte proliferation and migration, and negative regulation of matrix-degrading enzymes result in bone and cartilage recovery upon administration of MSCs-derived exosomes. Notwithstanding, insufficient quantity of isolated exosomes, lack of reliable potency test, and exosomes heterogeneity hurdle their application in clinics. Herein, we will deliver an outline respecting the advantages of MSCs-derived exosomes-based therapy in common bone- and joint-associated musculoskeletal disorders. Moreover, we will have a glimpse the underlying mechanism behind the MSCs-elicited therapeutic merits in these conditions.

Electromagnetic field therapy in cardiovascular diseases: A review of patents, clinically effective devices, and mechanism of therapeutic effects.

In recent years, electromagnetic field (EMF) therapy has gathered much attention for its protective effects on cardiovascular functions. From reviewing the literature, it is evident that exposure to specific EMF spectrums, such as static- and extremely low frequency (ELF)- EMFs, by EMF-generating devices can be considered as a safe method for therapeutic means in various cardiovascular diseases, including heart failure, cardiac arrhythmias, and hypertension. This review article will describe registered patents and non-invasive clinically effective devices that generate EMF to target various cardiovascular diseases based on their mechanism of therapeutic effects.

Glycemic profile variability: An independent risk factor for diabetic neuropathy in patients with type 2 diabetes.

BACKGROUND: Impaired glycemic control is a potential predictor for macro- and microvascular complications of diabetes, which could be recognized by glycemic variability. The aim of this 10-year prospective cohort study presented here is to gain a better understanding of the correlation between GV and diabetic peripheral neuropathy (DPN) as one of the most common complications of T2DM. METHODS: Since February 2010, 1152 adult patients with T2DM have been followed-up. Baseline features, anthropometric measurements, and laboratory findings were collected and documented during ten years. The association between DPN incidence and glycemic profile variability was evaluated using cox regression analysis. The coefficient of variation of glycemic indices within subjects was calculated and compared using an independent sample t-test. RESULTS: Individuals who developed neuropathy had significantly higher mean levels of glycemic indices (HbA1c, FBS, and 2hpp), urinary albumin excretion, mean creatinine levels, and a longer duration of diabetes. A significant positive correlation between incidence of DPN and glycemic profile variability (cv-FBS10 %, cv-FBS20 %, cv-2hpp20 %, cv-HbA1c5 % and cv-HbA1c10 %) was revealed. Results also showed that higher variability of FBS was associated with the higher risk of neuropathy incidence (HR: 12.29, p-value: 0.045), which indicates that glycemic profile variability is an independent risk factor for DPN in patients with T2DM. CONCLUSION: Variability of glycemic profiles from a visit to visit, regardless of sustained hyperglycemia, was indeed a significant risk factor for DPN in diabetic type 2 patients. CV-FBS was the most critical glycemic variability indices for DPN development.

Atherogenic index of plasma is an independent predictor of metabolic-associated fatty liver disease in patients with type 2 diabetes.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease, is the leading cause of liver disease that can ultimately lead to cirrhosis. Identifying a screening marker for early diagnosis of MAFLD in patients with type 2 diabetes (T2D) can reduce the risk of morbidity and mortality. This study investigated the association between the atherogenic index of plasma (AIP) and MAFLD in patients with T2D. METHOD: A retrospective case-control study was conducted and medical records of patients with T2D were assessed. The baseline characteristics, anthropometric indices, laboratory measurements including liver functions tests, fasting blood sugar, HbA1C, lipid profile were documented. RESULTS: Out of 2547 patients with T2D, 824 (32.4%) had MAFLD. The multivariate logistic regression analysis showed a significant difference in female-to-male ratio (1.11 vs. 1.33, OR = 0.347, P-value < 0.001), ALT (42.5 ± 28.1 vs. 22.4 ± 11.1, OR = 1.057, P-value < 0.001), and AIP (0.6 ± 0.3 vs. 0.5 ± 0.3, OR = 5.057, P-value < 0.001) between MAFLD and non-MAFLD groups, respectively. According to the AIP quartile, the prevalence of MAFLD increased significantly in patients with higher AIP quartiles (P-value < 0.001). Also, we found a cut-off of 0.54 for AIP in predicting MAFLD in patients with T2D (sensitivity = 57.8%, specificity = 54.4%). CONCLUSION: In this study, we found that AIP is a good and independent predictor for MAFLD in patients with T2D which could help physicians in early diagnosis and follow-up of patients with T2D.

Successful transvenous lead extraction of abandoned lead implanted through persistent left superior vena cava.

Persistent left superior vena cava, the most common thoracic venous anomaly, may complicate transvenous lead extraction (TLE). We report a successful case of TLE in a patient with persistent left superior vena cava, despite a long dwelling time and several pocket revisions due to pocket infection. The lead was removed via a hand-powered mechanical extraction sheath, and postoperative complications did not occur. Complicated TLE cases may have a better outcome if performed in a high-volume center with experienced specialists.

Transcranial direct current stimulation in patient with J wave syndrome and implantable cardioverter defibrillator.

J wave syndrome is a spectrum of proarrhythmic disorders including Brugada syndrome and early repolarization syndrome (ERS), that are prone to ventricular fibrillation and sudden cardiac death (SCD). In this case report we present a patient with ERS and aborted SCD complicated with cognitive impairment. We also investigated whether performing transcranial direct current stimulation to target his cognitive impairment, interfered with the function of his implantable cardioverter defibrillator.

Adverse reactions in a large cohort of patients with inborn errors of immunity receiving intravenous immunoglobulin.

BACKGROUND: Intravenous immunoglobulins (IVIg) are the major treatment in inborn errors of immunity (IEI) disorders; However, IVIg infusions show some adverse effects. We aimed to assess the adverse reactions of IVIg infusions. METHODS: Data of IVIg infusions in IEI patients were collected from 2011 to 2021. Totally, 363 IEI patients received IVIg regularly in Iran entered the study. The adverse reactions are classified regarding their severity and chronicity. RESULTS: 22,667 IVIg infusions were performed in the study. 157 patients (43.2%) and 1349 (5.9%) infusions were associated with at least one type of adverse reaction. The highest rates of adverse reactions were seen in severe combined immunodeficiency. Myalgia, chills, headache, fever, and hypotension were the most frequent adverse effects of IVIg. CONCLUSION: The reactions affect almost half of the patients mainly in the first infusions which necessitate the close observation of IEI patients receiving IVIg.