Citations

Abstract Objectives Right ventricular (RV) failure occurring after left ventricular assist device (LVAD) implantation is associated with increased mortality. Purpose We sought to determine whether RV strain by echocardiography predicts outcomes following LVAD. Methods Consecutive patients who underwent continuous flow LVAD placement at our clinic between February 2007 and October 2018 were included. Patients with complex congenital heart disease and arrhythmogenic right ventricular cardiomyopathy were excluded. Baseline characteristics, pre-operative hemodynamic catheterization (1 week) transthoracic echocardiography (1 month) measurements were obtained from the medical record. Speckle tracking RV free wall longitudinal 2D strain was measured using TomTec Imaging System. Univariate and multivariable analysis performed to identify predictors of mortality following LVAD. Results The study group was comprised of 323 patients (mean age 60.8±11.5, 79.9% male) of which 256 had adequate image quality for RV strain. RV strain was impaired in most patients (mean −11.7±3.47). RV strain of −8.1% was identified as predictive of poor outcomes. RV strain did not correlate with other measures of RV dysfunction including pulmonary artery pulsatility index (PAPi) and RVFAC. After adjusting for PAPi, RA pressure, and clinical cumulative risk scores (Matthews, Kormos and Lietz-Miller) impaired RV free wall longitudinal strain (OR: 1.14; 95% CI: 1.01–1.29, p=0.025), tricuspid regurgitation (by vena contracta width (TRvc) (OR: 1.19; 95% CI: 1.05–1.36, p=:0.0021) and smaller LVEDD (OR: 0.95; 95% CI: 0.92–0.99, p:0.023) predicted 30-day all-cause mortality and RV failure. Decreased RV free wall strain also predicted peri-operative mortality (22.58% vs. 4.89%, p=0.0003) and prolonged inotropic support (247.0.±277.4 vs. 122.8±139.3, p=0.024). Conclusions RV free wall strain is a non-invasive independent predictor of 30-day adverse outcomes (RV failure or all-cause mortality) Routine measurement of RV free strain may identify those patients at highest risk for early and long term mortality following LVAD. Funding Acknowledgement Type of funding source: None

Abstract Background Transmitral gradient (TMG) is highly dependent on hemodynamic state, leading to discordance between TMG and mitral valve area (MVA). The effect of heart rate (HR) and stroke volume (SV) on TMG among patients with mitral stenosis (MS) is poorly understood. Purposes We aimed to (1) develop a formula for projected TMG (proTMG) for assessment of MS severity under varying hemodynamics; (2) assess the prognostic value of proTMG in patients with MS. Methods All patients evaluated for suspected MS without ≥moderate other valve disorder at our tertiary center between 2001 and 2017 were analyzed. Projected TMG is the expected gradient under normal flow (SV 80–94 ml and HR 60–79 bpm), and was modeled based on the observed impact of HR and SV on TMG by multiple regression analysis. The data were randomly split (2:1) into training and testing sets. The improvement in agreement between MVA and proTMG was evaluated. Composite cardiac events including all-cause death and mitral valve interventions were compared according to TMG grade using TMG and proTMG. Severe and moderate MS were defined as MVA ≤1.5 cm2 and 1.5–2.0 cm2 respectively, by the continuity equation. MVA ≤1.0 cm2 was considered as very severe MS. Results Of 4973 patients with suspected MS (age 73±12 years, 33% male), severe MS was present in 437 (9%, including 98 with very severe MS) and moderate MS in 934 (19%). In 838 patients with normal HR and SV, very severe, severe and moderate MS corresponded to TMG ≥12 mmHg, ≥6 mmHg and 4–6 mmHg, respectively. In the training set (n=3315), the median [interquartile range] of HR and SV were 70 [61–80] bpm and 97 [83–113] mL in men (n=1120), and 72 [63–82] bpm and 84 [71–97] mL in women (n=2195), respectively. The impact of HR and SV on TMG for men and women were 0.07 and 0.08 mmHg per 1 bpm increase in HR (95% confidence interval [CI] 0.06–0.07 and 0.07–0.08), and 0.03 and 0.05 mmHg per 1 mL increase in SV (95% CI 0.03–0.03 and 0.04–0.05), respectively. Therefore, the final formula to calculate proTMG was: proTMG=TMG-0.07(HR-70)-0.03(SV-97) in men and proTMG=TMG-0.08(HR-72)-0.05(SV-84) in women. In the testing set (n=1658), the proTMG (kappa=0.63, 95% CI 0.60–0.66) had better agreement with MS severity by MVA than TMG (kappa=0.28, 95% CI 0.24–0.32). To explore the prevalence of patients reclassified using proTMG, in 98 with TMG ≥12 mmHg, proTMG remained ≥6 mmHg. Of 657 with TMG 6–12 mmHg, proTMG remained ≥6 mmHg in 356 (54%), and decreased to <6 mmHg in 301 (46%). In patients with TMG 6–12 mmHg, proTMG ≥6 mmHg was associated with higher probability of cardiac events compared with <6 mmHg during follow-up of 2.8±3.1 years (Figure). Conclusion We propose a novel concept of projected TMG defined as the expected transmitral gradient at normal HR and SV levels. This improved the diagnostic yield of Doppler TMG measurements for MS severity assessment and identified a low-risk subset of patients with elevated TMG due to high HR or SV. Funding Acknowledgement Type of funding source: None

Abstract Background Atrial fibrillation (Afib) leads to beat-to-beat variability in cycle length; however, whether there is associated beat-to-beat variability in the tricuspid annulus (TA) dimensions or variability in the time in cardiac cycle when TA reaches maximal size is unknown. Purpose We aim to assess the beat-to-beat variability in the TA dimensions in Afib compared with sinus rhythm (SR). Methods Images were obtained from 58 patients (29 in Afib, 29 in SR) undergoing either 3D TTE or TEE examination. We measured TA in 3–6 cardiac cycles per patient using commercially available software (TomTec 4MV). Results Median absolute difference in maximal TA area over 3–6 cardiac cycles was 1.60 cm2 (range 0.35 cm2 to 4.08 cm2) in Afib vs. 1.17 cm2 (range 0.32 cm2 to 2.19 cm2) in SR, p=0.0063. Median absolute difference in the maximal circumference was 0.79 cm (range 0.09 cm to 2.2 cm) in Afib vs 0.54 cm (range 0.12 cm to 1.43 cm) in SR, p=0.0175. A total of 118 cardiac cycles were analyzed in patients in SR and 147 in Afib. Timing of maximal TA area was most commonly recorded at end-diastole (80–100% of the R-R interval) in 62% of cycles in SR; however, it was distributed over a broad range in Afib, p<0.0001, [Figure]. Conclusion Afib leads to significant beat-to-beat variability in the maximal TA area, minimal TA area, maximal TA circumference, and in the time of maximal TA area. These findings suggest that accurate assessment of TA dimensions should be based on continuous tracking of the TA over several cardiac cycles, especially in patients with Afib. These observations have significant implications for device sizing in percutaneous tricuspid valve interventions. Timing of Maximal TA Area Funding Acknowledgement Type of funding source: None

Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking status and gender. Despite these advances BAL small and large extracellular vehicles (EVs) proteomes reveal aberrant protein expression in paracrine signaling mechanisms in cancer initiation and progression. We consequently present a case-control study of 24 bronchoalveolar lavage extracellular vesicle samples which were analyzed by state-of-the-art liquid chromatography-mass spectrometry (LC-MS). We obtained evidence that BAL EVs proteome complexity correlated with lung cancer stage 4 and mortality within two years´ follow-up (p value = 0.006). The potential therapeutic target DNMT3B complex is significantly up-regulated in tumor tissue and BAL EVs. The computational analysis of the immune and fibroblast cell markers in EVs suggests that patients who deceased within the follow-up period display higher marker expression indicative of innate immune and fibroblast cells (four out of five cases). This study provides insights into the proteome content of BAL EVs and their correlation to clinical outcomes.

AbstractBackgroundAscertaining involvement of left ventricular assist device (LVAD) in a patient presenting with bloodstream infection (BSI) can be challenging, frequently leading to use of chronic antimicrobial suppressive (CAS) therapy. We aimed to assess the efficacy of CAS therapy to prevent relapse of BSI from LVAD and non-LVAD sources.MethodsWe retrospectively screened adults receiving LVAD support from 2010 through 2018, to identify cases of BSI. Bloodstream infection events were classified into LVAD-related, LVAD-associated, and non-LVAD BSIs.ResultsA total of 121 episodes of BSI were identified in 80 patients. Of these, 35 cases in the LVAD-related, 14 in the LVAD-associated, and 46 in the non-LVAD BSI groups completed the recommended initial course of therapy and were evaluated for CAS therapy. Chronic antimicrobial suppressive therapy was prescribed in most of the LVAD-related BSI cases (32 of 35, 91.4%) and 12 (37.5%) experienced relapse. Chronic antimicrobial suppressive therapy was not prescribed in a majority of non-LVAD BSI cases (33, 58.9%), and most (31, 93.9%) did not experience relapse. Chronic antimicrobial suppressive therapy was prescribed in 9 of 14 (64.2%) cases of LVAD-associated BSI and none experienced relapse. Of the 5 cases in this group that were managed without CAS, 2 had relapse.ConclusionsPatients presenting with LVAD-related BSI are at high risk of relapse. Consequently, CAS therapy may be a reasonable approach in the management of these cases. In contrast, routine use of CAS therapy may be unnecessary for non-LVAD BSIs.

Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.