The interventricular conduction delays guide best cardiac resynchronization therapy: A tailored-patient approach to perform a CRT through Conduction System Pacing.

Evaluation of conduction intervals to predict success of resynchronization in biventricular pacing(BiVP) or Conduction System Pacing(CSP) is not spread in clinical practice. A right ventricle-to-left ventricle intrinsic conduction interval (RVs-LVs) > 70 ms or prolonged RVpaced - LVs(RVp-LVs)interval can predict Cardiac Resynchronization Therapy (CRT)response.This paper describes a case of cardiac resynchronization guided by spontaneous and paced interventricular conduction delays (IVCD) obtained in BiVP that led to changing intraoperative approach. A strategy for cardiac resynchronization based on the CSP/BiVP approach according to the IVCD could represent a viable and reliable solution to obtain a narrow paced QRS and to improve the CRT response.

Structural and Hemodynamic Changes of the Right Ventricle in PH-HFpEF.

One of the most important diagnostic challenges in clinical practice is the distinction between pulmonary hypertension (PH) due to primitive pulmonary arterial hypertension (PAH) and PH due to left heart diseases. Both conditions share some common characteristics and pathophysiological pathways, making the two processes similar in several aspects. Their diagnostic differentiation is based on hemodynamic data on right heart catheterization, cardiac structural modifications, and therapeutic response. More specifically, PH secondary to heart failure with preserved ejection fraction (HFpEF) shares features with type 1 PH (PAH), especially when the combined pre- and post-capillary form (CpcPH) takes place in advanced stages of the disease. Right ventricular (RV) dysfunction is a common consequence related to worse prognosis and lower survival. This condition has recently been identified with a new classification based on clinical signs and progression markers. The role and prevalence of PH and RV dysfunction in HFpEF remain poorly identified, with wide variability in the literature reported from the largest clinical trials. Different parenchymal and vascular alterations affect the two diseases. Capillaries and arteriole vasoconstriction, vascular obliteration, and pulmonary blood fluid redistribution from the basal to the apical district are typical manifestations of type 1 PH. Conversely, PH related to HFpEF is primarily due to an increase of venules/capillaries parietal fibrosis, extracellular matrix deposition, and myocyte hypertrophy with a secondary "arteriolarization" of the vessels. Since the development of structural changes and the therapeutic target substantially differ, a better understanding of pathobiological processes underneath PH-HFpEF, and the identification of potential maladaptive RV mechanisms with an appropriate diagnostic tool, become mandatory in order to distinguish and manage these two similar forms of pulmonary hypertension.

Left Ventricular Lead Placement for Biventricular Pacing in a Left Lateral Vein in a Patient with Congenital Atresia of the Coronary Sinus Ostium.

Coronary sinus ostial atresia (CSOA) is a rare kind of congenital heart anomaly. This creates a new drainage pathway for the cardiac venous flow, with the most common being a persistent left superior vena cava (PLSVC). During the implantation of a cardiac resynchronization therapy defibrillator, we discovered a case of CSOA in a patient who underwent aortic valve and ascending aorta replacement. CSOA led to the research and subsequent identification of a PLSVC, which drained in the CS. The left ventricular pacing lead was appropriately placed in a left lateral vein. This case report highlights the technical aspects and procedural difficulties that characterize this specific anatomical variant.

The role of fibrosis, inflammation, and congestion biomarkers for outcome prediction in candidates to cardiac resynchronization therapy: is "response" the right answer?

Background: Cardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT "response" and outcome. Our study investigated the long-term prognostic significance of cardiac biomarkers in HFrEF patients with an indication for CRT. Methods: Consecutive patients referred for CRT implantation were retrospectively evaluated. The soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), N-terminal portion of the B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured at baseline and after 1 year of follow-up. Multivariate analyses were performed to evaluate their correlation with the primary composite outcome of cardiovascular mortality and heart failure hospitalizations at a mean follow-up of 9 ± 2 years. Results: Among the 86 patients enrolled, 44% experienced the primary outcome. In this group, the mean baseline values of NT-proBNP, Gal-3, and sST2 were significantly higher compared with the patients without cardiovascular events. At the multivariate analyses, baseline Gal-3 [cut-off: 16.6 ng/ml, AUC: 0.91, p < 0.001, HR 8.33 (1.88-33.33), p = 0.005] and sST2 [cut-off: 35.6 ng/ml AUC: 0.91, p < 0.001, HR 333 (250-1,000), p = 0.003] significantly correlated with the composite outcome in the prediction models with high likelihood. Among the parameters evaluated at 1-year follow-up, sST2, eGFR, and the variation from baseline to 1-year of Gal-3 levels showed a strong association with the primary outcome [HR 1.15 (1.08-1.22), p < 0.001; HR: 0.84 (0.74-0.91), p = 0.04; HR: 1.26 (1.10-1.43), p ≤ 0.001, respectively]. Conversely, the echocardiographic definition of CRT response did not correlate with any outcome. Conclusion: In HFrEF patients with CRT, sST2, Gal-3, and renal function were associated with the combined endpoint of cardiovascular death and HF hospitalizations at long-term follow-up, while the echocardiographic CRT response did not seem to influence the outcome of the patients.

Right ventricular myocardial work for the prediction of early right heart failure and long-term mortality after left ventricular assist device implant.

AIMS: Right heart failure (RHF) after left ventricular assist device (LVAD) implant is burdened by high morbidity and mortality rates and should be prevented by appropriate patient selection. Adequate right ventricular function is of paramount importance but its assessment is complex and cannot disregard afterload. Myocardial work (MW) is a non-invasive Speckle Tracking Echocardiography-derived method to estimate pressure-volume loops. The aim of this study was to evaluate the performance of right ventricular myocardial work to predict RHF and long-term mortality after LVAD implant. METHODS AND RESULTS: Consecutive patients from May 2017 to February 2022 undergoing LVAD implant were retrospectively reviewed. Patients without a useful echocardiographic exam prior to LVAD implant were excluded. MW analysis was performed. The primary endpoints were early RHF (<30 days from LVAD implant) and death at latest available follow-up. We included 23 patients (mean age 64 ± 8 years, 91% men). Median follow-up was 339 days (IQR: 30-1143). Early RHF occurred in six patients (26%). A lower right ventricular global work efficiency [RVGWE, OR 0.86, 95% confidence intervals (CI) 0.76-0.97, P = 0.014] was associated with the occurrence of early RHF. Among MW indices, the performance for early RHF prediction was greatest for RVGWE [area under the curve (AUC) 0.92] and a cut-off of 77% had a 100% sensitivity and 82% specificity. At long-term follow-up, death occurred in 4 of 14 patients (28.6%) in the RVGWE > 77% group and in 6 of 9 patients (66.7%) in the RVGWE < 77% group (HR 0.25, 95% CI 0.07-0.90, P = 0.033). CONCLUSION: RVGWE was a predictor of early RHF after LVAD implant and brought prognostic value in terms of long-term mortality.

ADONHERS (Aged DONor HEart Rescue by Stress Echo) National Protocol: Recipient's Survival after 10-Year Follow-Up.

Background: The gold-standard treatment for end-stage heart failure is heart transplantation, but the lack of organ donors remains an important limitation in this field. An accurate selection of marginal hearts is fundamental to increase organ availability. Purpose: In our study we analyzed if recipients receiving marginal donor (MD) hearts, selected by dipyridamole stress echocardiography according to the ADOHERS national protocol, had different outcomes compared to recipients with acceptable donor (AD) hearts. Methods: Data were collected and retrospectively analyzed from patients who received an orthotopic heart transplant at our institution between 2006 and 2014. Dipyridamole stress echo was performed on identified marginal donors and selected hearts were eventually transplanted. Clinical, laboratory and instrumental features of the recipients were evaluated and patients with homogenous baseline characteristics were selected. Results: Eleven recipients transplanted with a selected marginal heart and eleven recipients transplanted with an acceptable heart were included. Mean donor age was 41 ± 23. The median follow-up was 113 months (IQR 86-146 months). Age, cardiovascular risk and morpho-functional characteristics of the left ventricle were comparable between the two populations (p > 0.05). Left atrial size was significantly higher in patients with marginal hearts (acceptable atrial volume: 23 ± 5 mL; marginal atrial volume: 38 ± 5 mL; p = 0.003). Acceptable donor recipients showed a higher impact of Cardiac Allograph Vasculopathy (p = 0.019). No rejection differences were found between the two groups. Four patients deceased, three were standard donor recipients and one was from the marginal donor group. Conclusions: Our study shows how cardiac transplant (Htx) from selected marginal donor hearts through a non-invasive bedside technique can alleviate the shortage of organs without a difference in survival compared to acceptable donor hearts.

Pressure-strain loops unveil haemodynamics behind mechanical circulatory support systems.

AIMS: Mechanical circulatory support (MCS) systems are increasingly employed in cardiogenic shock and advanced heart failure. A thorough understanding of the complex interactions occurring among heart, vasculature, and device is essential to optimize patient's management. The aim of this study is to explore non-invasive haemodynamic profiling of patients undergoing MCS based on pressure-strain (PS) analysis. METHODS: Clinical and echocardiographic data from consecutive patients undergoing different MCS systems positioning/implantation admitted to the third level cardiological intensive care unit of Siena Hospital from August 2021 to November 2021 were retrospectively reviewed. Patients without a useful echocardiographic exam or without arterial blood pressure recording at the time of echocardiography were excluded. Myocardial work analysis was performed in the included patients. RESULTS: We reviewed 18 patients, of which nine were excluded. Included patients were three patients with intra-aortic balloon pump (IABP), two patients with durable left ventricular assist device (dLVAD), two patients with Impella®, one patient with extracorporeal membrane oxygenation (ECMO), and one patient with ECMO and IABP. Myocardial work analysis was feasible in each included patient. The use of IABP shifted the PS curve rightward and downward. Global work index (GWI) and global wasted work (GWW) decreased after IABP positioning, whereas global work efficiency (GWE) increased. The use of continuous-flow pumps, whether temporaneous (Impella®) or long term (dLVAD), induced a change in the PS loop morphology, with a shift towards a triangular shape. ECMO positioning alone resulted in a narrowing of the PS loop, with a decrease in GWI and GWE and an increase in GWW and mean arterial pressure. The combined used of IABP with ECMO widened the PS loop and improved GWI and GWE. CONCLUSIONS: PS loops analysis in patients undergoing MCS seems to be feasible and may unveil MCS-induced haemodynamic variations. Myocardial work could be used to monitor ventricular-arterial-device coupling and guide tailored MCS management.

Vericiguat in Heart Failure: Characteristics, Scientific Evidence and Potential Clinical Applications.

Despite recent advances in heart failure (HF) management, the risk of death and hospitalizations remains high in the long term. HF is characterized by endothelial dysfunction, inflammation and increased oxidative stress, due to a reduction in the activity of the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway. All these factors contribute to direct damage at the myocardial, vascular and renal level. Vericiguat restores the deficiency in this signaling pathway, through stimulation and activation of sGC, aiming to increase cGMP levels, with a reduction in HF-related oxidative stress and endothelial dysfunction. Two main clinical trials were developed in this setting: the SOCRATES-REDUCED phase II study and the VICTORIA phase III study. They found that vericiguat is safe, well tolerated and effective with an absolute event-rate reduction in patients affected by HF with reduced ejection fraction (HFrEF) and recent cardiac decompensation. In patients with HF with preserved ejection fraction (HfpEF), the SOCRATES-PRESERVED trial demonstrated an improvement in quality of life and health status, but the proven beneficial effects with vericiguat are still limited. Further studies are needed to correctly define the role of this drug in heart failure syndromes. Our paper reviews the potential applications and pharmacological characteristics of vericiguat in HFrEF and HFpEF.

Diastolic function in heart transplant: From physiology to echocardiographic assessment and prognosis.

Heart transplant (HTx) still represents the most effective therapy for end-stage heart failure, with a median survival time of 10 years. The transplanted heart shows peculiar physiology due to the profound alterations induced by the operation, which inevitably influences several echocardiographic parameters assessed during these patients' follow-ups. With these premises, the diastolic function is one of the main aspects to take into consideration. The left atrium (LA) plays a key role in this matter, and that same chamber is significantly impaired with the transplant, with different degrees of altered function based on the surgical technique. Therefore, the traditional echocardiographic evaluation of diastolic function applied to the general population might not properly reflect the physiology of the graft. This review attempts to provide current evidence on diastolic function in HTx starting from defining its different physiology and how the standard echocardiographic parameters might be affected to its prognostic role. Furthermore, based on the experience of our center and the available evidence, we proposed an algorithm that might help clinicians distinguish from actual diastolic dysfunction from a normal diastolic pattern in HTx population.

Correlation of left ventricular myocardial work indices with invasive measurement of stroke work in patients with advanced heart failure.

Objectives: This study aimed to explore the correlation between left ventricular (LV) myocardial work (MW) indices and invasively-derived LV stroke work index (SWI) in a cohort of patients with advanced heart failure (AHF) considered for heart transplantation. Background: Left ventricular MW has emerged as a promising tool for diagnostic and prognostic purposes in heart failure (HF) but its relationship with hemodynamic data derived from right heart catheterization (RHC) has not been assessed in patients with advanced heart failure yet. Materials and methods: Consecutive patients with AHF considered for heart transplantation from 2016 to 2021 performing RHC and echocardiography as part of the workup were included. Conventional LV functional parameters and LV MW indices, including LV global work index (GWI), LV global constructive work (GCW), LV global wasted work (GWW), LV global work efficiency (GWE), and other were calculated and compared with invasively-measured LV SWI. Results: The population included 44 patients. Median time between RHC and echocardiography was 0 days (IQR: 0-24). Median age was 60 years (IQR: 54-63). For the most part, etiology of HF was non-ischemic (61.4%) and all patients were either on class NYHA II (61.4%) or III (27.3%). Median left ventricular ejection fraction was 25% (IQR: 22.3-32.3), median NT-proBNP 1,377 pg/ml (IQR: 646-2570). LV global longitudinal strain (GLS) significantly correlated with LV SWI (r = -0.337; p = 0.031), whereas, LV ejection fraction (EF) did not (r = 0.308; p = 0.050). With regard to LV MW indices, some of them demonstrated correlation with LV SWI, particularly LV GWI (r = 0.425; p = 0.006), LV GCW (r = 0.506; p = 0.001), LV global positive work (LV GPW; r = 0.464; p = 0.003) and LV global systolic constructive work (GSCW; r = 0.471; p = 0.002). Conclusion: Among LV MW indices, LV GCW correlated better with invasively-derived SWI, potentially representing a powerful tool for a more comprehensive evaluation of myocardial function.