Antiarrhythmic and Anti-Inflammatory Effects of Sacubitril/Valsartan on Post-Myocardial Infarction Scar.

BACKGROUND: Sacubitril/valsartan (Sac/Val) is superior to angiotensin-converting enzyme inhibitors in reducing the risk of heart failure hospitalization and cardiovascular death, but its mechanistic data on myocardial scar after myocardial infarction (MI) are lacking. The objective of this work was to assess the effects of Sac/Val on inflammation, fibrosis, electrophysiological properties, and ventricular tachycardia inducibility in post-MI scar remodeling in swine. METHODS: After MI, 22 pigs were randomized to receive ß-blocker (BB; control, n=8) or BB+Sac/Val (Sac/Val, n=9). The systemic immune response was monitored. Cardiac magnetic resonance data were acquired at 2-day and 29-day post MI to assess ventricular remodeling. Programmed electrical stimulation and high-density mapping were performed at 30-day post MI to assess ventricular tachycardia inducibility. Myocardial samples were collected for histological analysis. RESULTS: Compared with BB, BB+Sac/Val reduced acute circulating leukocytes (P=0.009) and interleukin-12 levels (P=0.024) at 2-day post MI, decreased C-C chemokine receptor type 2 expression in monocytes (P=0.047) at 15-day post MI, and reduced scar mass (P=0.046) and border zone mass (P=0.043). It also lowered the number and mass of border zone corridors (P=0.009 and P=0.026, respectively), scar collagen I content (P=0.049), and collagen I/III ratio (P=0.040). Sac/Val reduced ventricular tachycardia inducibility (P=0.034) and the number of deceleration zones (P=0.016). CONCLUSIONS: After MI, compared with BB, BB+Sac/Val was associated with reduced acute systemic inflammatory markers, reduced total scar and border zone mass on late gadolinium-enhanced magnetic resonance imaging, and lower ventricular tachycardia inducibility.

Cardiac electronic implantable devices: A call for a new coding system.

Over the last decades, cardiac electronic implantable devices (CEID) have incorporated a myriad of technological capabilities that are not conveniently inferred by using the conventional ICHD and NBG coding systems. We propose a new coding system (i.e., the C-ARL-A coding system) aimed at overcoming this important limitation.

Biophysical Tissue Characterization of Ventricular Tachycardia Substrate With Local Impedance Mapping to Predict Critical Sites.

BACKGROUND: New tools are needed to improve ventricular tachycardia (VT) substrate characterization and optimize outcomes. LI provides biophysical tissue characterization. OBJECTIVES: The purpose of this study was to test local impedance (LI)-based mapping to predict critical ventricular tachycardia components after myocardial infarction (MI). METHODS: One month after a nonreperfused anterior MI, endo-epicardial high-density electroanatomic mapping and endocardial LI mapping were performed in 23 Landrace Large X White pigs. LI thresholds were set using the blood pool value to define a 10 Ω range: low (blood pool +9Ω). RESULTS: Low LI was detected in low-voltage areas in 100% of cases, but intermediate LI was found in both core (87%) and border zone (12.5%) voltage areas. A total of 17 VTs were induced (VT isthmus identified in 9 animals). VT inducibility was associated with the size of intermediate LI area (OR: 1.19 [95% CI: 1.0-1.4]; P = 0.039) and the presence of specific LI patterns: LI corridor (OR: 15.0 [95% CI: 1.3-169.9]; P = 0.029); LI gradient (OR: 30.0 [95% CI: 2.1-421.1]; P = 0.012), high LI heterogeneity (OR: 21.7 [95% CI: 1.8-260.6]; P = 0.015), and presence of ≥2 low LI regions (OR: 11.3 [95% CI: 1.0-130.2]; P = 0.053). Potential VT isthmuses were in areas of intermediate LI and colocalized to LI patterns associated with VT inducibility in all cases (LI corridors or LI gradient). Low LI regions did not actively participate in the VT circuit (0%). CONCLUSIONS: LI mapping is feasible and may add useful characterization of the VT substrate. Specific LI patterns (ie, corridors, gradients) were associated with VT inducibility and colocalized with the VT isthmus, thus representing a potential new target for ablation in substrate-based procedures.

Inefficient diastolic filling in dual-chamber pacemaker recipients: impact of atrio-ventricular interval shortening (AVI-SHORT study).

BACKGROUND: Adequate synchronization between the passive ("E") and active ("a") left ventricular (LV) diastolic filling contributes to the efficiency of the heartbeat. E/a superposition in dual-chamber pacemaker (PM) recipients is an under-recognized phenomenon that may be corrected by shortening the atrio-ventricular interval (AVI). We aimed at establishing the prevalence of E/a superposition in PM patients and to analyze the clinical, echocardiographic, and biological impact of AVI shortening. METHODS: Seventy patients with dual-chamber PMs (74 ± 8 years old, 12 women) were consecutively enrolled in this study. Patients with baseline E/a superposition were crossed over from default to manually shortened AVI or vice versa in a case-control fashion (intervention group). Patients without baseline E/a superposition (controls) served as a reference for a descriptive comparison with the intervention group. RESULTS: Thirty-three patients had E/a superposition after PM implantation (47%). Controls (n = 37) had higher LV ejection fraction (59 ± 8% vs. 53 ± 10%, p = 0.048) and lower levels of high sensitive troponin T and ST2 (p < 0.05) than intervention group patients. The AVI was shortened at 48 ± 9 ms in order to ensure adequate E/a separation. The walked distance increased from 75 ± 17 to 78 ± 10% (p = 0.049) and the Euro-QoL score from 0.50 ± 0.27 to 0.63 ± 0.19 (p = 0.011) with short AVI. CONCLUSIONS: E/a superposition occurs in approximately half of dual-chamber PM recipients and is associated with reduced LV function and increased myocardial injury biomarkers. AVI shortening produces a modest but significant effect in functional capacity and quality of life.

Electrophysiological effects of adipose graft transposition procedure (AGTP) on the post-myocardial infarction scar: A multimodal characterization of arrhythmogenic substrate.

Objective: To assess the arrhythmic safety profile of the adipose graft transposition procedure (AGTP) and its electrophysiological effects on post-myocardial infarction (MI) scar. Background: Myocardial repair is a promising treatment for patients with MI. The AGTP is a cardiac reparative therapy that reduces infarct size and improves cardiac function. The impact of AGTP on arrhythmogenesis has not been addressed. Methods: MI was induced in 20 swine. Contrast-enhanced magnetic resonance (ce-MRI), electrophysiological study (EPS), and left-ventricular endocardial high-density mapping were performed 15 days post-MI. Animals were randomized 1:1 to AGTP or sham-surgery group and monitored with ECG-Holter. Repeat EPS, endocardial mapping, and ce-MRI were performed 30 days post-intervention. Myocardial SERCA2, Connexin-43 (Cx43), Ryanodine receptor-2 (RyR2), and cardiac troponin-I (cTnI) gene and protein expression were evaluated. Results: The AGTP group showed a significant reduction of the total infarct scar, border zone and dense scar mass by ce-MRI (p = 0.04), and a decreased total scar and border zone area in bipolar voltage mapping (p < 0.001). AGTP treatment significantly reduced the area of very-slow conduction velocity (<0.2 m/s) (p = 0.002), the number of deceleration zones (p = 0.029), and the area of fractionated electrograms (p = 0.005). No differences were detected in number of induced or spontaneous ventricular arrhythmias at EPS and Holter-monitoring. SERCA2, Cx43, and RyR2 gene expression were decreased in the infarct core of AGTP-treated animals (p = 0.021, p = 0.018, p = 0.051, respectively). Conclusion: AGTP is a safe reparative therapy in terms of arrhythmic risk and provides additional protective effect against adverse electrophysiological remodeling in ischemic heart disease.

Inappropriate sinus tachycardia in post-COVID-19 syndrome.

Inappropriate sinus tachycardia (IST) is a common observation in patients with post-COVID-19 syndrome (PCS) but has not yet been fully described to date. To investigate the prevalence and the mechanisms underlying IST in a prospective population of PCS patients. Consecutive patients admitted to the PCS Unit between June and December 2020 with a resting sinus rhythm rate ≥ 100 bpm were prospectively enrolled in this study and further examined by an orthostatic test, 2D echocardiography, 24-h ECG monitoring (heart rate variability was a surrogate for cardiac autonomic activity), quality-of-life and exercise capacity testing, and blood sampling. To assess cardiac autonomic function, a 2:1:1 comparative sub-analysis was conducted against both fully recovered patients with previous SARS-CoV-2 infection and individuals without prior SARS-CoV-2 infection. Among 200 PCS patients, 40 (20%) fulfilled the diagnostic criteria for IST (average age of 40.1 ± 10 years, 85% women, 83% mild COVID-19). No underlying structural heart disease, pro-inflammatory state, myocyte injury, or hypoxia were identified. IST was accompanied by a decrease in most heart rate variability parameters, especially those related to cardiovagal tone: pNN50 (cases 3.2 ± 3 vs. recovered 10.5 ± 8 vs. non-infected 17.3 ± 10; p < 0.001) and HF band (246 ± 179 vs. 463 ± 295 vs. 1048 ± 570, respectively; p < 0.001). IST is prevalent condition among PCS patients. Cardiac autonomic nervous system imbalance with decreased parasympathetic activity may explain this phenomenon.

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model.

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization and cardiovascular drugs, a significant proportion of patients develop pathological left-ventricular remodeling and progressive heart failure following MI. Therefore, new therapeutic options, such as cellular and gene therapies, among others, have been developed to repair and regenerate injured myocardium. In this context, animal models of MI are crucial in exploring the safety and efficacy of these experimental therapies before clinical translation. Large animal models such as swine are preferred over smaller ones due to the high similarity of swine and human hearts in terms of coronary artery anatomy, cardiac kinetics, and the post-MI healing process. Here, we aimed to describe an MI model in pig by permanent coil deployment. Briefly, it comprises a percutaneous selective coronary artery cannulation through retrograde femoral access. Following coronary angiography, the coil is deployed at the target branch under fluoroscopic guidance. Finally, complete occlusion is confirmed by repeated coronary angiography. This approach is feasible, highly reproducible, and emulates the pathogenesis of human non-revascularized MI, avoiding the traditional open-chest surgery and the subsequent postoperative inflammation. Depending on the time of follow-up, the technique is suitable for acute, sub-acute, or chronic MI models.

Atrioventricular Node Ablation to Enhance Resynchronization Therapy Response in a Patient With Complete Atrioventricular Block.

Up to one-third of patients who undergo cardiac resynchronization therapy do not obtain clinical benefit. A systematic approach can identify treatable causes in many nonresponding patients. We present a case of nonresponse to cardiac resynchronization therapy that resolved by ablation of the atrioventricular node in a patient with complete atrioventricular block. (Level of Difficulty: Advanced.).

Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest.

BACKGROUND: Growth differentiation factor 15 (GDF-15) is an inflammatory cytokine released in response to tissue injury. It has prognostic value in cardiovascular diseases and other acute and chronic conditions. Here, we explored the value of GDF-15 as an early predictor of neurologic outcome after an out-of-hospital cardiac arrest (OHCA). METHODS: Prospective registry study of patients in coma after an OHCA, admitted in the intensive cardiac care unit from a single university center. Serum levels of GDF-15 were measured on admission. Neurologic status was evaluated according to the cerebral performance category (CPC) scale. The relationship between GDF-15 levels and poor neurologic outcome at 6 months was analyzed. RESULTS: Among 62 patients included, 32 (51.6%) presented poor outcome (CPC 3-5). Patients with CPC 3-5 exhibited significantly higher GDF-15 levels (median, 17.1 [IQR, 11.1-20.4] ng/mL) compared to those with CPC 1-2 (7.6 [IQR, 4.1-13.1] ng/mL; p = 0.004). Multivariable logistic regression analyses showed that age (OR, 1.09; 95% CI 1.01-1.17; p = 0.020), home setting arrest (OR, 8.07; 95% CI 1.61-40.42; p = 0.011), no bystander cardiopulmonary resuscitation (OR, 7.91; 95% CI 1.84-34.01; p = 0.005), and GDF-15 levels (OR, 3.74; 95% CI 1.32-10.60; p = 0.013) were independent predictors of poor outcome. The addition of GDF-15 in a dichotomous manner (≥ 10.8 vs. < 10.8 ng/mL) to the resulting clinical model improved discrimination; it increased the area under the curve from 0.867 to 0.917, and the associated continuous net reclassification improvement was 0.90 (95% CI 0.48-1.44), which allowed reclassification of 37.1% of patients. CONCLUSIONS: After an OHCA, increased GDF-15 levels were an independent, early predictor of poor neurologic outcome. Furthermore, when added to the most common clinical factors, GDF-15 improved discrimination and allowed patient reclassification.

Ventricular fibrillation in a patient with Wolff-Parkinson-White syndrome unrelated to pre-excited atrial fibrillation.

A 52-year-old man was admitted due to out-hospital cardiac arrest. Recurrent ventricular fibrillation (VF) occurred under therapeutic hypothermia thereafter. Previously inadverted full pre-excitation was documented exclusively and immediately prior to 4 out of the 5 VF relapses. Coronary vasospasm and early repolarization were also documented. An electrophysiological study demonstrated poor anterograde conduction over a left-sided accessory pathway. We theorize that maximum pre-excitation favored in-hospital VF by augmenting the repolarization vulnerability induced by therapeutic hypothermia, with coronary vasospasm accounting as the probable cause of out-hospital VF. A plausible VF mechanism in WPW syndrome unrelated to pre-excited atrial fibrillation is discussed.

Differences in neurohormonal activity partially explain the obesity paradox in patients with heart failure: The role of sympathetic activation.

BACKGROUND: Obese patients with chronic Heart Failure (HF) have better outcome than their lean counterparts, although little is known about the pathophysiology of this obesity paradox. Our aim was to evaluate the hypothesis that patients with chronic HF and obesity (defined as body mass index (BMI)≥30kg/m(2)), may have an attenuated neurohormonal activation in comparison with non-obese patients. METHODS AND RESULTS: The present study is the post-hoc analysis of a cohort of 742 chronic HF patients from a single-center study evaluating sympathetic activation by measuring baseline levels of norepinephrine (NE). Obesity was present in 33% of patients. Higher BMI and obesity were significantly associated with lower NE levels in multivariable linear regression models adjusted for covariates (p<0.001). Addition to NE in multivariate Cox proportional hazard models attenuated the prognostic impact of BMI in terms of outcomes. Finally, when we explored the prognosis impact of raised NE levels (>70th percentile) carrying out a separate analysis in obese and non-obese patients we found that in both groups NE remained a significant independent predictor of poorer outcomes, despite the lower NE levels in patients with chronic HF and obesity: all-cause mortality hazard ratio=2.37 (95% confidence interval, 1.14-4.94) and hazard ratio=1.59 (95% confidence interval, 1.05-2.4) in obese and non-obese respectively; and cardiovascular mortality hazard ratio=3.08 (95% confidence interval, 1.05-9.01) in obese patients and hazard ratio=2.08 (95% confidence interval, 1.42-3.05) in non-obese patients. CONCLUSION: Patients with chronic HF and obesity have significantly lower sympathetic activation. This finding may partially explain the obesity paradox described in chronic HF patients.