Updates on Baroreflex Activation Therapy and Vagus Nerve Stimulation for Treatment of Heart Failure With Reduced Ejection Fraction.

In the last decade, neuromodulation via baroreflex activation therapy (BAT) and vagus nerve stimulation (VNS) has emerged as an innovative approach for the treatment of heart failure with reduced ejection fraction (HFrEF). A review of the literature was conducted to examine the latest efficacy and safety data on neuromodulation for the treatment of HFrEF. Two independent researchers searched the PubMed, clinicaltrials.org, and the Cochrane databases for the most recent data on BAT and VNS published between 2013 and 2019. A total of nine studies were identified. BAT and VNS therapy consistently improved subjective heart failure parameters including New York Heart Association class and Minnesota Living with Heart Failure Questionnaire. Improvements in objective cardiac parameters such as left ventricular ejection fraction (LVEF) were less consistently seen; however, where present, ranged from +3% to +6%, in line with improvements seen after other guideline directed therapy such as left ventricular assist device (LVAD). Benefits of BAT showed a predilection for patients without cardiac resynchronization therapy (CRT) and efficacy of VNS therapy varied with device type. The clinical application of BAT and VNS was found to be limited due to low-powered data, inconsistencies in study design, short-term follow-up and lack of diversity in patient recruitment. Well-powered studies with consistent design, longer follow-up and diverse populations are warranted before BAT and VNS can be incorporated into heart failure guidelines and clinical practice.

Expression of Interleukin-17, Tumor Necrosis Factor-Alpha, and Matrix Metalloproteinase-8 in Patients with Chronic Peri-Implant Mucositis.

BACKGROUND The present study aimed to evaluate whether non-surgical treatment interferes with clinical parameters and local patterns of osteo-immunoinflammatory mediators (IL-17 and TNF-alpha) and matrix metalloproteinase-8 (MMP-8) that are found in peri-implant crevicular fluid (PICF) and biofilms during the progression of peri-implant mucositis. MATERIAL AND METHODS We selected 30 patients with peri-implant caused mucositis before (MP) and after treatment (TP) and 30 healthy people (HP) for the analysis of IL-17, TNF-alpha cytokine, and MMP-8 production in PICF and for analysis of colonization dynamics of periodontopathogenic bacteria in supra- and subgingival plaque samples. The levels of IL-17 and MMP-8 concentrations in samples were assayed by enzymatic immunosorbent assay (ELISA) and TNF-alpha levels were determined by enzyme amplified sensitivity immunoassay (EASIA) method in PICF. The micro-IDent test was used to detect 11 species of periodontopathogenic bacteria in subgingival biofilm. RESULTS We found significantly (P<0.001) higher levels of IL-17, TNF-alpha, and MMP-8 in the PICF of the MP and TP groups in comparison to the HP group. A significant association was found in MP associated with Parvimonas micra, as TNF-alpha in PICF was significantly higher (P=0.034) than in patients without Parvimonas micra. TNF-alpha levels in the samples of PICF showed a moderate correlation with clinical parameters, including plaque index (PI) (P=0.007) and MMP-8 levels (P=0.001), in the MP group. CONCLUSIONS Assessment of levels of inflammatory cytokines in PICF can aid in the identification of peri-implant mucositis, which can assist in early diagnosis, prevention, and treatment.

Clinical predictors of antitachycardia pacing response in implantable cardioverter defibrillator patients.

BACKGROUND: Antitachycardia pacing (ATP) provides safe and painless termination of reentrant ventricular arrhythmias in patients with implantable cardioverter defibrillator (ICDs), improving their quality of life. Established predictors of ATP responsiveness are not well known; only longer ventricular tachycardia (VT) cycle length and higher ejection fraction have been found to predict ATP success. OBJECTIVE: To investigate clinical and ECG predictors of ATP response in ICD patients with monomorphic VT. METHODS: The ICD clinic database was searched for monomorphic VT events requiring ICD therapy in patients with ischemic or non-ischemic cardiomyopathy. Each patient's first ICD encounter for VT was assessed. Patient demographics, clinical characteristics, VT rate, and ATP responsiveness (always, sometimes, and never successful) were recorded. An ECG was analyzed for QRS morphology and duration. Data was assessed for predictors of ATP responsiveness. RESULTS: In 527 patients, characteristics associated with always successful ATP included ACE-I/ARB therapy and slower VT rate (never successful ATP 197 ± 28 bpm, sometimes successful ATP 190 ± 27 bpm, always successful ATP 183 ± 22 bpm, P < .0001). Secondary prevention indication, amiodarone therapy, and longer QRS duration were associated with ATP failure. After multivariate analysis, only faster VT rate and amiodarone therapy were predictive of ATP failure. CONCLUSIONS: Neither QRS morphology nor duration was predictive of ATP success. Slower VT rate was predictive of repeated ATP responsiveness. Amiodarone therapy, which is known to increase VT cycle length, interestingly was associated with ATP failure for unclear reasons. More individualized and possibly more aggressive ATP programming may be warranted in patients on amiodarone.

Peripheral Blood Leukocytes Interleukin-1 Beta (IL-1ß) Cytokine Hyper-Reactivity in Chronic Periodontitis.

BACKGROUND Levels of pro-inflammatory cytokine (IL-1ß) released by peripheral blood leukocyte medium (PBLM), isolated from chronic periodontitis patients (P) before therapy and matched to controls, were determined in the presence or absence of non-opsonized Escherichia coli and Staphylococcus aureus. MATERIAL AND METHODS In this investigation, 26 patients with untreated, severe, generalized, chronic periodontitis and 26 healthy subjects (H) were enrolled. Periodontal status was assessed by measuring bleeding on probing (BOP), clinical attachment loss (CAL), probing pocket depth (PPD), and Ramfjord index (PDI). The levels of IL-1ß (µg/ml) were assayed by a standard Immunoenzymetric Assay Diasource IL-1ß ELISA kit in PBLM. RESULTS Our study showed that the values of IL-1ß levels in PBLM of the P group (stimulated with non-opsonized E. coli and S. aureus) were significantly higher than in the analogous medium of H group subjects (P<0.001). All correlations between the cytokine levels of IL-1ß in the samples of PBLM (stimulated with non-opsonized E. coli and S. aureus) and clinical parameters such as BOP, PPD, CAL, and PDI were significantly higher in the group of patients with periodontitis. CONCLUSIONS Levels of IL-1ß secreted by leukocytes may help measure severe, generalized, chronic periodontitis, and can be predictive of future detrimental clinical sequelae associated with chronic periodontitis.

The healthcare utilization and cost of treating patients experiencing inappropriate implantable cardioverter defibrillator shocks: a propensity score study.

BACKGROUND: Inappropriate shocks (IASs) from implantable cardioverter defibrillators (ICDs) are associated with decreased quality of life, but whether they increase healthcare utilization and treatment costs is unknown. We sought to determine the impact of IASs on subsequent healthcare utilization and treatment costs. METHODS: We conducted a case-control analysis of ICD patients at a single institution from 1997 to 2010 and who had ≥12 months of post-ICD implant follow-up. Cases included all patients experiencing an IAS during the first 12 months after implantation. Eligible control patients did not receive a shock of any kind during the 12 months after implantation. Propensity scores based on 36 covariates (area under curve = 0.78) were used to match cases to controls. We compared the rate (occurrences/person year [PY]) of healthcare utilization immediately following IAS to the end of the 12-month follow-up period to the rate in the no-shock group over 12 months of follow-up. We also compared 12-month postimplant treatment (outpatient clinic, emergency room, and hospitalization) costs in both groups. RESULTS: A total of 76 patients experiencing ≥1 IAS during the first 12 months after implant (contributing 48 PYs) were matched to 76 no-shock patients (contributing 76 PYs). Cardiovascular (CV)-related clinic visit and hospitalization rates were increased following an IAS compared to those not receiving a shock (4.0 vs 3.3 and 0.7 vs 0.5, respectively, P = 0.02 for both). CV-related emergency room visitation (0.15 vs 0.08) rates were also numerically higher following an IAS, but did not reach statistical significance (P = 0.26). Patients experiencing an IAS accrued greater treatment costs during the 12 months postimplant compared to no-shock patients ($13,973 ± $46,345 vs $6,790 ± $19,091, P = 0.001). CONCLUSION: Recipients of IAS utilize the healthcare system more frequently following an IAS than patients not experiencing a shock. This increased utilization results in higher costs of treating IAS patients during the 12 months postimplant.

A comparison of outcomes for patients receiving implantable cardioverter defibrillators for primary vs secondary-prevention.

OBJECTIVE: Compare characteristics and outcomes of patients receiving implantable cardioverter defibrillators (ICDs) for primary vs secondary cardiac arrest prevention. METHODS: Patients in this cohort study were identified from a prospectively collected ICD database from June 1999 to August 2003 and divided into groups based on whether they received their ICD for primary or secondary-prevention of cardiac arrest. Patient follow-up continued until August of 2006 and the occurrence of appropriate ICD shocks, inappropriate ICD shocks, and mortality were compared between groups. RESULTS: Of the 437 patients, 80.8% were male, 70.3% had coronary disease, and the mean age was 65.7+/-13.1 years. At baseline, primary-prevention patients had lower left ventricular ejection fraction (LVEF), use of a single chamber device and utilization of beta blockers and antiarrhythmics while having a greater use of biventricular pacing as compared to secondary-prevention patients. Over the first 12 months after implantation, the primary-prevention group was 43.0% less likely to receive an appropriate shock for ventricular arrhythmias (P=0.002) and 34.2% less likely to have an appropriate shock over the entire follow-up period (P=0.018). The incidence of inappropriate ICD shocks over the first 12 months after implantation and over the entire follow-up period was similar between groups (P=0.900 and P=0.217, respectively) as was mortality (P=0.228 and P=0.757, respectively). CONCLUSIONS: Primary-prevention patients are characteristically different in numerous ways from secondary-prevention patients, but despite having a greater risk of experiencing appropriate shocks, exhibit a similar risk of inappropriate shocks and mortality over an average follow-up time exceeding 41 months.

Effects of ischemia on repolarization in patients with single and multivessel coronary disease.

To evaluate if QT dispersion (QTd) may be affected by the number of obstructed coronary arteries (CAs) in patients with acute myocardial infarction (MI) and undergoing angioplasty, and to evaluate if QTd may be affected by ejection function of the heart. The infarct related CA was identified by coronary angiography in 141 patients (97 men, mean age 61.6 +/- 12.9 years) with acute MI undergoing percutaneous angioplasty. Successful reperfusion was defined as TIMI III flow with < 20% residual stenosis. QTd, calculated by subtracting the shortest from the longest QT interval on 12-lead electrocardiograms, was examined immediately before and after angioplasty, at 24 hours, and 3 days after angioplasty. Successful reperfusion was achieved in 98 (69.5%) patients. Prolonged QTd at baseline was found in all patients with ischemia. A trend toward a decrease in QTd was observed immediately after angioplasty and at 24 hours, and a significant decrease at 3 days in patients with successful reperfusion regardless of the number of occluded CAs. There was no change in QTd found in patients with no reperfusion. An increase in QTd was observed in patients with acute ischemia due to single or multivessel disease.

The immediate and short-term effect of successful percutaneous coronary intervention on repolarization in acute myocardial infarction patients.

OBJECTIVES: The primary objective was to assess the immediate and short-term impact of successful percutaneous coronary intervention (PCI) on QT dispersion (QT disp) and corrected QT dispersion (QTc disp). Secondarily, the impact of PCI on QT and QTc disp within different infarct-related arteries and the impact of successful PCI in these different arteries were evaluated. METHODS: Patients (n = 140, age 61.6 +/- 12.9, 69% male) undergoing direct primary PCI for acute MI were evaluated. Twelve-lead ECGs were obtained before (baseline), immediately after (0 h), 24hours after, and 3 days after PCI. The QT and QTc interval in each of the 12-leads were measured and the shortest interval was subtracted from the longest to derive the QT disp and QTc disp, respectively. RESULTS: Angiography showed blockages in the left anterior descending, right coronary artery, and circumflex in 37.1, 48.9, and 15.0% of patients, respectively. Overall, 97 patients achieved successful reflow. QT and QTc disp were significantly improved in the group with successful reflow at each follow-up time after PCI versus baseline and corresponding values in the unsuccessful reflow group. QT disp was improved among patients with successful reflow irrespective of which infarct artery was responsible for the acute myocardial infarction. CONCLUSIONS: Successful reflow with PCI is associated with a rapid reduction in QT disp and QTc disp that is maintained for at least 3 days after the event. Conversely, unsuccessful reflow was not associated with significant reductions in QT or QTc disp.