Preclinical assessment of the feasibility, safety and lesion durability of a novel 'single-shot' pulsed field ablation catheter for pulmonary vein isolation.

AIMS: Single-shot pulmonary vein isolation can improve procedural efficiency. To assess the capability of a novel, expandable lattice-shaped catheter to rapidly isolate thoracic veins using pulsed field ablation (PFA) in healthy swine. METHODS AND RESULTS: The study catheter (SpherePVI; Affera Inc) was used to isolate thoracic veins in two cohorts of swine survived for 1 and 5 weeks. In Experiment 1, an initial dose (PULSE2) was used to isolate the superior vena cava (SVC) and the right superior pulmonary vein (RSPV) in six swine and the SVC only in two swine. In Experiment 2, a final dose (PULSE3) was used for SVC, RSPV, and left superior pulmonary vein (LSPV) in five swine. Baseline and follow-up maps, ostial diameters, and phrenic nerve were assessed. Pulsed field ablation was delivered atop the oesophagus in three swine. All tissues were submitted for pathology. In Experiment 1, all 14/14 veins were isolated acutely with durable isolation demonstrated in 6/6 RSPVs and 6/8 SVC. Both reconnections occurred when only one application/vein was used. Fifty-two and 32 sections from the RSPVs and SVC revealed transmural lesions in 100% with a mean depth of 4.0 ± 2.0 mm. In Experiment 2, 15/15 veins were isolated acutely with 14/15 veins (5/5 SVC, 5/5 RSPV, and 4/5 LSPV) durably isolated. Right superior pulmonary vein (31) and SVC (34) sections had 100% transmural, circumferential ablation with minimal inflammation. Viable vessels and nerves were noted without evidence of venous stenosis, phrenic palsy, or oesophageal injury. CONCLUSION: This novel expandable lattice PFA catheter can achieve durable isolation with transmurality and safety.

Role of biomarkers of cardiac remodeling, myofibrosis, and inflammation in assessment of disease severity in euvolemic patients with chronic stable heart failure.

OBJECTIVE: This study aimed to determine the importance of biomarkers of chronic heart failure (CHF) for assessing disease severity in euvolemic stable patients. PATIENTS AND METHODS: N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, galectin-3, cystatin-C, soluble suppression of tumorigenicity 2 (sST2), tissue type inhibitor of matrix metalloproteinase (TIMP)-1, and ceruloplasmin levels were measured in euvolemic patients with stable CHF. Severity of CHF was defined by echocardiographic and biochemical parameters. RESULTS: In 160 patients (123 men and 37 women, mean age: 65.8±12.2 years), we found strong associations between NT-proBNP and bilirubin levels (r = 0.434) and the estimated glomerular filtration rate (r = -0.321). GDF-15 and cystatin-C levels were significantly correlated with parameters of kidney function. In multivariable regression analysis, NT-proBNP levels were associated with the left ventricular ejection fraction and left ventricular end-systolic volume (coefficient of determination R2 = 0.777). Additionally, GDF-15 levels were correlated with urea levels (R2 = 0.742), and cystatin C levels were correlated with urea and bilirubin levels (R2 = 0.732). CONCLUSION: Besides NT-proBNP, GDF-15 and cystatin C are promising biomarkers for establishing the severity of disease in euvolemic patients with stable CHF.

Focal Pulsed Field Ablation for Pulmonary Vein Isolation and Linear Atrial Lesions: A Preclinical Assessment of Safety and Durability.

BACKGROUND: A novel ablation and mapping system can toggle between delivering biphasic pulsed field (PF) and radiofrequency energy from a 9-mm lattice-tip catheter. We assessed the preclinical feasibility and safety of (1) focal PF-based thoracic vein isolation and linear ablation, (2) combined PF and radiofrequency focal ablation, and (3) PF delivered directly atop the esophagus. METHODS: Two cohorts of 6 swine were treated with pulsed fields at low dose (PFLD) and high dose (PFHD) and followed for 4 and 2 weeks, respectively, to isolate 25 thoracic veins and create 5 right atrial (PFLD), 6 mitral (PFHD), and 6 roof lines (radiofrequency+PFHD). Baseline and follow-up voltage mapping, venous potentials, ostial diameters, and phrenic nerve viability were assessed. PFHD and radiofrequency lesions were delivered in 4 and 1 swine from the inferior vena cava onto a forcefully deviated esophagus. All tissues were submitted for histopathology. RESULTS: Hundred percent of thoracic veins (25 of 25) were successfully isolated with 12.4±3.6 applications/vein with mean PF times of <90 seconds/vein. Durable isolation improved from 61.5% PFLD to 100% with PFHD (P=0.04), and all linear lesions were successfully completed without incurring venous stenoses or phrenic injury. PFHD sections had higher transmurality rates than PFLD (98.3% versus 88.1%; P=0.03) despite greater mean thickness (2.5 versus 1.3 mm; P<0.001). PF lesions demonstrated homogenous fibrosis without epicardial fat, nerve, or vessel involvement. In comparison, radiofrequency+PFHD sections revealed similar transmurality but expectedly more necrosis, inflammation, and epicardial fat, nerve, and vessel involvement. Significant ablation-related esophageal necrosis, inflammation, and fibrosis were seen in all radiofrequency sections, as compared with no PF sections. CONCLUSIONS: The lattice-tip catheter can deliver focal PF to durably isolate veins and create linear lesions with excellent transmurality and without complications. The PF lesions did not damage the phrenic nerve, vessels, and the esophagus.

Inappropriate shocks in the subcutaneous ICD: Incidence, predictors and management.

BACKGROUND: The entirely subcutaneous implantable cardioverter-defibrillator (S-ICD) eliminates the need for transvenous leads, and therefore has the potential to improve lead-longevity and reduce lead-related complications. The S-ICD has a morphology-based sensing algorithm of which inappropriate shocks have been reported. METHODS: We analyzed the incidence, predictors and management of inappropriate shocks in the EFFORTLESS S-ICD Registry, which collects S-ICD implantation information and follow-up data from clinical centers in Europe and New Zealand. RESULTS: During a follow-up of 21 ± 13 months, 48 out of 581 S-ICD patients (71% male, age 49 ± 18 years) experienced 101 inappropriate shocks (8.3%). The most common cause was cardiac signal oversensing (73%), such as T-wave oversensing. Eighteen shocks (18%) were due to supraventricular tachycardias (SVT), of which 15 occurred in the shock-only zone. Cox-proportional hazard modeling using time-dependent covariates demonstrated that patients with a history of atrial fibrillation (HR 2.4) and patients with hypertrophic cardiomyopathy (HR 4.6) had an increased risk for inappropriate shocks, while programming the primary vector for sensing (from xyphoid to V6) reduced the risk. Reprogramming or optimization of SVT treatment after the first clinical event of inappropriate shock was successful in preventing further inappropriate shocks for cardiac oversensing and SVT events. CONCLUSIONS: Inappropriate shocks, mainly due to cardiac oversensing, occurred in 8.3% of the S-ICD patients. Patients with hypertrophic cardiomyopathy or a history of atrial fibrillation were at increased risk, warranting specific attention for sensing and programming in this population.

Assessment of left ventricular diastolic function by radionuclide ventriculography in patients with chronic heart failure and reduced ejection fraction.

STUDY OBJECTIVE: To compare parameters of diastolic function as assessed by radionuclide ventriculography (RNVG) and Doppler echocardiography (ECHO) in the patients with chronic heart failure and reduced ejection fraction (HF REF). PATIENTS AND METHODS: RNVG and ECHO were performed on the same day in 40 patients with systolic chronic HF, NYHA II and III, with LV EF < 50 % and sinus rhythm, followed at tertiary HF clinic. Diastolic function was assessed by RNVG using parameters: PFR (peak filling rate [% SV/sec]), TFR - time to peak filling rate (ms), and by ECHO using pulse Doppler parameters: the peak Doppler velocities of early (E) and late diastolic flow (A), the E/A ratio, the calculated mean of the early (E´) diastolic velocity of septal and lateral mitral annulus measured by tissue Doppler imaging, and the E/E´ ratio. RESULTS: The mean PFR was 421.7 (median 371.0) % SV/sec and TPF was 198.7 ms (median 169.5), the mean E/A ratio was 1.21 (median 0.85) and the E/E´ ratio was 9.0 (median 8.40). TPF correlated significantly (inverse correlation) with the E/A ratio (r = -0.34, p = 0.030), and not significantly with E´ (r = -0.27, p = 0.082), the PFR/age ratio correlated with the E/E´ ratio (r = -0.31, p = 0.05). CONCLUSION: Significant correlations of parame-ters of diastolic function as assessed by radionuclide and Doppler studies were identified in the HF REF patients.

Noninvasive assessment of hemodynamic variables using near-infrared spectroscopy in patients experiencing cardiogenic shock and individuals undergoing venoarterial extracorporeal membrane oxygenation.

PURPOSE: The relationship between near-infrared spectroscopy cerebral oximetry (CrSO2), peripheral oximetry (PrSO2) and hemodynamic variables is not fully understood. METHODS: The relationship between CrSO2/PrSO2 and cardiac index (CI), systemic vascular resistance index (SVRI) and mean arterial pressure (MAP) in patients experiencing cardiogenic shock and those undergoing venoarterial extracorporeal membrane oxygenation (ECMO) was retrospectively analyzed; in patients on ECMO, total circulatory index (TCI) was calculated from the sum of CI and extracorporeal blood flow index. RESULTS: In patients experiencing cardiogenic shock (n=10), significant correlations between PrSO2 values and CI (Spearman r=0.81; P<.0001), SVRI (r=-0.45; P<.0001), and MAP (r=0.58; P<.0001) were found. Significant correlations between CrSO2 and CI (r=0.55; P<.0001) and SVRI (r=-0.47; P<.0001), but not MAP, were observed. Linear regression analysis revealed that CI could be calculated using the following equation: CI=PrSO2/24.0. In patients on VA ECMO (n=12), significant correlations were found between PrSO2 and TCI (r=0.68; P<.0001), SVRI (r=-0.47; P<.0001), and MAP (r=0.27; P=.025). Significant correlations were also found between CrSO2 and TCI (r=0.68; P<.0001) and SVRI (r=-0.51; P<.0001), but not MAP. CONCLUSIONS: Results of the present study suggest that CrSO2 and PrSO2 in particular can be used for noninvasive estimation and monitoring of global circulatory status in patients experiencing cardiogenic shock and individuals undergoing ECMO.