Left ventricular fibrosis as a main determinant of filling pressures and left atrial function in advanced heart failure.

AIMS: Advanced heart failure (AdHF) is characterized by variable degrees of left ventricular (LV) dysfunction, myocardial fibrosis, and raised filling pressures which lead to left atrial (LA) dilatation and cavity dysfunction. This study investigated the relationship between LA peak atrial longitudinal strain (PALS), assessed by speckle-tracking echocardiography (STE), and invasive measures of LV filling pressures and fibrosis in a group of AdHF patients undergoing heart transplantation (HTX). METHODS AND RESULTS: We consecutively enrolled patients with AdHF who underwent HTX at our Department. Demographic and basic echocardiographic data were registered, then invasive intracardiac pressures were obtained from right heart catheterization, and STE was also performed. After HTX, biopsy specimens from explanted hearts were collected to quantify the degree of LV myocardial fibrosis. Sixty-four patients were included in the study (mean age 62.5 ± 11 years, 42% female). The mean LV ejection fraction (LVEF) was 26.7 ± 6.1%, global PALS was 9.65 ± 4.5%, and mean pulmonary capillary wedge pressure (PCWP) was 18.8 ± 4.8 mmHg. Seventy-three % of patients proved to have severe LV fibrosis. Global PALS was inversely correlated with PCWP (R = -0.83; P < 0.0001) and with LV fibrosis severity (R = -0.78; P < 0.0001) but did not correlate with LVEF (R = 0.15; P = 0.2). Among echocardiographic indices of LV filling pressures, global PALS proved the strongest [area under the curve 0.955 (95% confidence interval 0.87-0.99)] predictor of raised (>18 mmHg) PCWP. CONCLUSION: In patients with AdHF, reduced global PALS strongly correlated with the invasively assessed LV filling pressure and degree of LV fibrosis. Such relationship could be used as non-invasive indicator for optimum patient stratification for therapeutic strategies.

Technology and technique for left ventricular assist device optimization: A Bi-Tech solution.

BACKGROUND: We investigated the synergistic effect of the new cone-bearing design of Jarvik 2000 (Jarvik Heart Inc., NY) together with a minimally-invasive approach to outcomes of LVAD patients. METHODS: We retrospectively reviewed all patients from 5 institutions involved in the Jarvik 2000 Italian Registry, from October 2008 to October 2016. Patients were divided into three groups according to pump design and implantation technique: pin-bearing design and conventional approach (Group 1); cone-bearing and conventional approach (Group 2); cone-bearing and minimally-invasive implantation (Group 3). RESULTS: A total of 150 adult patients with end-stage heart failure were enrolled: 26 subjects in Group 1, 74 in Group 2, and 50 in Group 3. Nineteen patients (73%) in Group 1, 51 (69%) in Group 2, and 36 (72%) in Group 3 were discharged. During follow-up, 22 patients underwent transplantation, while in 3 patients the LVAD was explanted. The overall 1-year survival was 58 ± 10%, 64 ± 6%, and 74% ± 7% in Groups 1, 2, and 3, respectively (p = 0.034). The competing-risks-adjusted cumulative incidence rate for adverse events was 42.1 [27-62.7] per 100 patient-years in Group 1, 35.4 [25.3-48.2] in Group 2, and 22.1 [12.4-36.4] in Group 3 (p = 0.046 for Group 1 vs. 3). CONCLUSIONS: The association of the modern cone-bearing configuration of Jarvik 2000 and minimally invasive surgery improved survival and minimized the risk for cardiovascular events, as a result of combining technology and technique.

Left atrial strain by speckle tracking predicts atrial fibrosis in patients undergoing heart transplantation.

AIMS: In patients with heart failure (HF), chronically raised left ventricular (LV) filling pressures lead to progressive left atrial (LA) dysfunction and fibrosis. We aimed to assess the correlation of LA reservoir strain (peak atrial longitudinal strain, PALS) by speckle tracking echocardiography (STE) and LA fibrosis assessed by myocardial biopsy in patients undergoing heart transplantation (HTx). METHODS AND RESULTS: Forty-eight patients with advanced HF [mean age 51.2 ± 8.1 years, 29% females; LV ejection fraction ≤25% and New York Heart Association (NYHA) class III-IV] referred for HTx were enrolled and underwent pre-operative echocardiographic evaluation, right heart catheterization, and cardiopulmonary exercise testing. Exclusion criteria were non-sinus rhythm, mechanical ventilation, severe mitral/tricuspid regurgitation, or other valvular disease and poor acoustic window. After HTx, LA bioptic samples were collected and analysed to determine the extent of myocardial fibrosis (%). LA fibrosis showed correlation with PALS (R = -0.88, P < 0.0001), VO2max (R = -0.68, P < 0.0001), NYHA class (R = 0.66, P < 0.0001), LA stiffness (R = 0.58, P = 0.0002), and E/e' (R = 0.44, P = 0.005), while poorly correlated with E/A ratio (R = 0.23, P = 0.21). PALS had a good correlation with NYHA class (R = -0.64, P < 0.0001), PAoP (R = -0.61, P = 0.03) and VO2max (R = 0.57, P = 0.0001). Multivariate regression analysis identified PALS (beta = -0.91, P < 0.001) and LA Volume (beta = -0.19, P = 0.03) as predictors of LA Fibrosis, while E/e' was not a significant predictor (beta = 0.15, P = 0.08). CONCLUSION: Emerging as a possible index of myocardial fibrosis in patients with advanced HF, PALS could help to optimize the management and the selection of those patients with irreversible LA structural damage for advanced therapeutic strategies.

Systematic Left Ventricular Assist Device Implant Eligibility with Non-Invasive Assessment: The SIENA Protocol.

In patients with end-stage left ventricular (LV) heart failure who receive LV assist device (LVAD) implantation, right ventricular (RV) failure represents a possible critical complication that heavily affects morbidity and mortality. Several clinical, laboratory, hemodynamic, and echocardiographic variables have been found to be associated with RV failure occurrence after surgery. Different models and risk scores have been proposed, with poor results. No accordance has ever been reached about RV pre-operative evaluation, and time has come to introduce a standardized systematic protocol for LVAD suitability assessment according to RV function. We analyzed imaging parameters associated with LVAD implantation-related RV failure, in order to identify the minimum number for pre-operative reliable prediction of post-operative RV failure. A few echocardiographic parameters have been identified as the most reliable, or promising, and reproducible tools in this field: free-wall RV longitudinal strain, RV fractional area change, RV sphericity index, and RV ejection fraction with 3D-echocardiography. We propose the Systematic LVAD Implant Eligibility with Non-invasive Assessment protocol-the SIENA protocol-as a new and simple way of pre-operative evaluation of patients candidates to LVAD implantation.

From bench to bedside: Can the improvements in left ventricular assist device design mitigate adverse events and increase survival?

OBJECTIVE: In vitro tests demonstrated that the new cone-bearing configuration of the Jarvik 2000 (Jarvik Heart Inc, New York, NY) left ventricular assist device exhibits better hydraulic efficiency than the previous pin-bearing design. We investigated the long-term outcomes of patients who received the Jarvik 2000 left ventricular assist device, depending on bearing design. METHODS: A retrospective review of prospectively collected data from 18 centers included in the Italian Registry was performed. From May 2008 to September 2013, 99 patients with end-stage heart failure were enrolled. Patients were divided into 2 groups according to their Jarvik 2000 suspending mechanism: Group pin included patients with pin bearings (May 2008 to June 2010), and group cone included patients with newer cone bearings (July 2010 to September 2013). The 2 groups did not differ significantly in terms of baseline characteristics. RESULTS: A total of 30 of 39 patients (group pin) and 46 of 60 patients (group cone) were discharged. During follow-up, 6 patients underwent transplantation, and in 1 patient the left ventricular assist device was explanted. The cumulative incidence competing risk of the entire cohort for noncardiovascular-related death was 28% (20%-40%); the cumulative incidence competing risk for cardiovascular-related death was 56% (42%-73%): 71% in group pin versus 26% in group cone (P = .034). The multivariate analyses confirmed that the pin-bearing design was a risk factor for cardiovascular death, along with Interagency Registry for Mechanically Assisted Circulatory Support class. Right ventricular failures and ischemic and hemorrhagic strokes were significantly higher in group pin. CONCLUSIONS: Patients with the new pump configuration showed a better freedom from cardiovascular death and lower incidence of fatal stroke and right ventricular failure. Further studies are needed to prove the favorable impact of pump-enhanced fluid dynamics on long-term results.

RV Longitudinal Deformation Correlates With Myocardial Fibrosis in Patients With End-Stage Heart Failure.

OBJECTIVES: This study was performed to determine the accuracy of right ventricular (RV) longitudinal strain (LS) in predicting myocardial fibrosis in patients with severe heart failure (HF) undergoing heart transplantation. BACKGROUND: RVLS plays a key role in the evaluation of its systolic performance and clinical outcome in patients with refractory HF. METHODS: We studied 27 patients with severe systolic HF (ejection fraction ≤25% and New York Heart Association functional class III to IV, despite full medical therapy and cardiac resynchronization therapy) using echocardiography before heart transplantation. RV free wall LS, right atrial LS, sphericity index (SI), and tricuspid annular plane systolic excursion (TAPSE) were all measured. Upon removal of the heart, from the myocardial histologic analysis, the ratio of the fibrotic to the total sample area determined the extent of fibrosis (%). RESULTS: RV myocardial fibrosis correlated with RV free wall LS (r = 0.80; p < 0.0001), SI (r = 0.42; p = 0.01) and VO2 max (r = -0.41; p = 0.03), with a poor correlation with TAPSE (r = -0.34; p = 0.05) and right atrial LS (r = -0.37; p = 0.03). Stepwise multivariate analysis showed that RV free wall LS (ß = 0.701, p < 0.0001) was independently associated with RV fibrosis (overall model R(2) = 0.64, p < 0.0001). RV free wall LS was the main determinant of myocardial fibrosis. In the subgroup of patients with severe RV fibrosis, RV free wall LS had the highest diagnostic accuracy for detecting severe myocardial fibrosis (area under the curve = 0.87; 95% confidence interval: 0.80 to 0.94). CONCLUSIONS: In late-stage HF patients, the right ventricle is enlarged, with reduced systolic function due to significant myocardial fibrosis. RV free wall myocardial deformation is the most accurate functional measure that correlates with the extent of RV myocardial fibrosis and functional capacity.

Left ventricular twist in clinically stable heart transplantation recipients: a speckle tracking echocardiography study.

BACKGROUND AND AIM: Cavity twist is an integral part of LV function and its pattern in transplanted hearts is not well known. This study aimed at exploring LV twist in clinically stable heart transplant (HT) recipients with no evidence for rejection. METHODS: We studied 32 HT patients (54 ± 24 months after HT), 34 other cardiac surgery (CS) patients and compared them with 35 health controls using speckle tracking echocardiography, measuring peak twist angle, time-to-peak twist, and untwist rate. RESULTS: LV twist angle was smaller in the HT group (6.2 ± 3.3°) in comparison with the CS group and controls (13.2 ± 3.5° and 13.1 ± 4.5°, respectively; p<0.0001 for all) and untwist rate was reduced (HT group: -74 ± 30°/s; CS group: -118 ± 43°/s; controls: -116 ± 39°/s; p<0.0001 for all). Time-to-peak twist was not different between groups. Time after HT was the main independent predictor of both LV twist angle and untwist rate (ß=0.8, p<0.0001). CONCLUSION: Though clinically stable, LV twist dynamics are significantly impaired in HT recipients, even in comparison with patients who underwent other cardiac surgery.