Smaller Left Ventricular End-diastolic Diameter Research Articles

Predicting impaired cardiopulmonary exercise capacity in patients with atrial fibrillation using a simple echocardiographic marker

BackgroundExercise intolerance is a common symptom associated with atrial fibrillation (AF). However, echocardiographic markers that can predict impaired exercise capacity are lacking. ObjectiveThis study aimed to investigate the association between echocardiographic parameters and exercise capacity assessed by cardiopulmonary exercise testing in patients with AF. MethodsThis single-center prospective study enrolled patients with AF who underwent echocardiography and cardiopulmonary exercise testing to evaluate exercise capacity at a tertiary center for AF management from 2020 to 2022. Patients with valvular heart disease, reduced left ventricular ejection fraction, or documented cardiomyopathy were excluded. ResultsOf the 188 patients, 134 (71.2%) exhibited impaired exercise capacity (peak oxygen consumption ≤85%), including 4 (2.1%) having poor exercise capacity (peak oxygen consumption <50%). Echocardiographic findings revealed that these patients had an enlarged left atrial end-systolic diameter (LA); smaller left ventricular end-diastolic diameter (LVEDD); and increased relative wall thickness, tricuspid regurgitation velocity, and LA/LVEDD and E/e′ ratios. In addition, they exhibited lower peak systolic velocity of the mitral annulus and LA reservoir strain. In the multivariate regression model, LA/LVEDD remained the only significant echocardiographic parameter after adjustment for age, sex, and body mass index (P = .020). This significance persisted even after incorporation of heart rate reserve, N-terminal pro-B-type natriuretic peptide level, and beta-blocker use into the model. ConclusionIn patients with AF, LA/LVEDD is strongly associated with exercise capacity. Further follow-up and validation are necessary to clarify its clinical implications in patient care.

Risk factors for immediate and delayed cardiogenic shock in patients with ventricular septal rupture after myocardial infarction

BackgroundVentricular septal rupture (VSR) is a serious complication occurring after myocardial infarction (MI). Cardiogenic shock (CS) is a common complication of VSR and an important factor affecting its prognosis. CS can occur in either an immediate or delayed manner after VSR; however, studies on the risk factors associated with immediate or delayed CS are scarce.MethodsWe retrospectively studied patients diagnosed with VSR after MI and admitted to the West China Hospital between September 2009 and August 2023. Demographic data, medical history, physical examination results, electrocardiograms, and echocardiographic and hematological data were extracted from electronic medical records or archived records. CS was defined as hypotension (&amp;lt;90 mmHg) and/or the requirement for catecholamines, pulmonary congestion, and signs of end-organ failure. The CS onset time was defined as the time at which catecholamines were initiated.ResultsA total of 88 patients with VSR after MI, including 49 males (55.7%), were enrolled. The average age was 70.2 years. Of these patients, 32 (36.4%) who already had CS at the time of VSR discovery were defined as immediate CS, and 28 (31.8%) who developed CS within 2 weeks after VSR discovery were defined as delayed CS. A smaller left ventricular end-diastolic diameter (LVEDD) and VSR discovered after admission were independent risk factors for immediate CS. Elevated heart rate and higher levels of creatine kinase-MB isoenzyme on admission were independent risk factors for delayed CS in patients without immediate CS after VSR.ConclusionsThe occurrence of CS in patients with VSR after MI has an evident time course. Thus, an early identification of patients at risk of immediate or delayed CS and optimization of treatment procedures may help improve the prognosis.

Does Size Matter for Female Continuous-flow LVAD Recipients? A Translational Approach to a Decade Long Question.

Females have increased risk of right-ventricular failure (RVF) and 3 month mortality after left-ventricular assist device (LVAD) implantation. In this translational study, we tested the hypothesis that sex differences in outcomes are driven by pump-induced LV size-volume mismatch, due to a negative impact on interventricular septal (IVS) interdependence. Adult continuous-flow LVAD recipients from the International Society For Heart And Lung Transplantation Mechanically Assisted Circulatory Support registry (n = 15,498) were studied to determine association of female sex with outcomes of 3 month mortality and RVF. Female sex was associated with smaller preimplant left-ventricular end-diastolic diameter (6.5 vs. 6.9 cm, p < 0.001), increased 3 month mortality (odds ratio [OR]: 1.42, p < 0.001) and RVF (OR: 1.18, p = 0.005). Smaller left-ventricular end-diastolic diameter was associated with worse outcomes after LVAD implantation (OR for mortality: 1.20, p < 0.001; RVF: 1.09, p < 0.001), and attenuated the association of female sex with these outcomes. In test bench heart phantoms (n = 4), the IVSs of smaller hearts demonstrated abnormal leftward shift earlier than larger hearts (volume change at IVS shift: 40 [95% confidence interval: 30-52] vs. 50 [95% confidence interval: 48-69] ml). Smaller LV size partially mediates worse post-LVAD outcomes for female patients, due to lower volume thresholds for adverse IVS shifting.

Left ventricular remodeling after mitral valve repair and papillary muscle approximation.

Mitral valve repair with papillary muscle approximation (MVr-PMA) for severe secondary mitral regurgitation (MR) decreases MR recurrence compared with MVr alone. This study assessed the effects of MVr-PMA on left ventricular (LV) remodeling and shape, systolic function and strain mechanics. Forty-eight patients who underwent MVr-PMA for severe secondary MR and had follow-up echocardiograms available for review were identified. Student's t-test, linear regression modeling, and receiver-operating characteristic curves were used in the statistical analyses. Median follow-up time was 14.9 months. MVr-PMA was associated with significant LV reverse remodeling with a smaller LV end-diastolic diameter, Systolic Sphericity Index, and interpapillary muscle distance at follow-up. Nine patients (18.8%) experienced moderate recurrent MR. When compared to recurrent MR patients at follow-up, those with durable MVr-PMA had a greater LV ejection fraction (32.8 vs. 22.0%, P=0.03), a smaller end-diastolic diameter (59.6 vs. 67.3 mm, P=0.03), Systolic Sphericity Index (0.35 vs. 0.47, P=0.03), and end-systolic interpapillary muscle distance (16.3 vs. 21.1 mm, P=0.03). A durable MVr-PMA also resulted in stable global longitudinal strain when compared with pre-operative values, while the recurrent MR group experienced a further decline (no recurrent MR: -8.4 vs. -7.5%; recurrent MR: -8.2 vs. -5.4%; P<0.05). A pre-operative LV end-diastolic diameter ≥ 64 mm was a discriminative predictor of MR recurrence (sensitivity=100%, specificity=51%, AUC=0.756, P=0.02). A durable MVr-PMA confers improved LV geometry and function, and stable LV mechanics. The extent of baseline LV remodeling identifies patients at risk for recurrent MR.

Gender Differences in Mortality After Left Ventricular Assist Device Implant: A Causal Mediation Analysis Approach.

We used the International Society for Heart and Lung Transplantation (ISHLT) Registry for Mechanically Assisted Circulatory Support (IMACS) database to examine 1) gender differences in post-left ventricular assist device (LVAD) mortality in the contemporary era and 2) preimplant clinical factors that might mediate any observed differences. Adults who received continuous-flow (CF)-LVAD from January 2013 to September 2017 (n = 9,565, age: 56.2 ± 13.2 years, 21.6% female, 31.1% centrifugal pumps) were analyzed. An inverse probability weighted Cox proportional hazards model was used to estimate association of female gender with all-cause mortality, adjusting for known covariates. Causal mediation analysis was performed to test plausible preimplant mediators mechanistically underlying any association between female gender and mortality. Females had higher mortality after LVAD (adjusted hazard ratio [HR]: 1.36; p < 0.0001), with significant gender × time interaction (p = 0.02). An early period of increased risk was identified, with females experiencing a higher risk of mortality during the first 4 months after implant (adjusted HR: 1.74; p < 0.0001), but not after (adjusted HR: 1.18; p = 0.16). More severe tricuspid regurgitation and smaller left ventricular end-diastolic diameter at baseline mediated ≈21.9% of the increased early hazard of death in females; however, most of the underlying mechanisms remain unexplained. Therefore, females have increased mortality only in the first 4 months after LVAD implantation, partially driven by worsening right ventricular dysfunction and LV-LVAD size mismatch.

Outcomes of Restrictive Cardiomyopathy Following LVAD Placement: An IMACS Analysis

Background Outcomes of patients with advanced heart failure (HF) due to restrictive cardiomyopathy (RCM) remain unfavorable in spite of advances in HF therapies. Left ventricular assist devices (LVADs) are a standard therapeutic option for patients with advanced HF, however there is limited data to support LVAD implantation in these patients. The purpose of this study was to examine outcomes in patients with end-stage RCM following LVAD implantation when compared with those with dilated cardiomyopathies (DCM). Methods The International Registry for Mechanically Assisted Circulatory Support (IMACS) registry was queried for all patients with RCM (n = 179) and DCM (n = 15,335) who underwent durable LVAD implantation between January 2013 and September 2017. Patients with RCM were grouped into amyloidosis, sarcoidosis, radiotherapy, idiopathic and other forms of RCM. Baseline patient characteristics, survival, and adverse events were compared among the groups. Results Patients with RCM had a mean age of 56 years and were predominately male (78.9%). Echocardiograms of patients with RCM had significantly smaller left ventricular end-diastolic diameter (LVEDD) compared to DCM (6.3 cm vs 6.8 cm p Conclusions In this analysis of an international registry, we demonstrated that patients with RCM have similar outcomes compared with patients with DCM following LVAD implantation. This observation invites future prospective investigations on validating our findings and on identifying challenges in regards to LVAD implantation in patients with advanced HF due to RCM.

Outcomes in Patients with Smaller Left Ventricular End Diastolic Diameter Following HeartMate 3 (HM3) Left Ventricular Assist Device (LVAD) Implantation

Outcomes in patients with small left ventricular end diastolic diameter (LVEDD) following HM3 LVAD implantation have not been well characterized. We sought to compare the clinical outcomes of patients with small LVEDD to those with dilated left ventricles. Patients who received a HeartMate 3 LVAD at our institution between October 1, 2015 and June 30, 2019 were analyzed. Patients who received a HM3 LVAD as a pump exchange were excluded. The cohort was divided in 2 groups: smaller LVEDD (≤60 mm in males and ≤58 mm in females) and larger LVEDD (>60 mm in males and >58 mm in females). One hundred and nineteen patients underwent HeartMate 3 LVAD implantation at our institution. Patients in the smaller LVEDD group (n: 22) had a mean LVEDD of 55.7±5 mm and patients in the larger LVEDD group had a mean LVEDD of 70.6±8 mm (p=<0.0001). Patients in the smaller LVEDD group tended to be older (60±11 vs 56±11 years, p=0.07), and included more males (82% vs. 68%, p=0.3) and fewer African-Americans (59% vs. 79%, p=0.08). Patients in the smaller LVEDD group were more likely to have a history of ischemic cardiomyopathy (50% vs. 23%, p=0.01), CAD (82% vs. 30%, p<0.001)) and diabetes (73% vs. 47%, p=0.03). INTERMACS class 1 + 2 was similar between groups (72% vs. 68%, p=0.9). Mean days on the ventilator (2.4±3 vs. 3.2±5 days, p=0.5), on inotropes (16±12 vs. 15±8 days, p=0.69) and vasopressors (9±9 vs. 7±11 days, p=0.6) was similar between groups. Mean length of stay (25±14 vs. 29±17 days, p=0.2) and readmissions days (25±52 vs. 27±46 days, p=0.8) were also similar. One-year survival was 90% for the smaller LVEDD group and 95% for the larger LVEDD group (Figure, log rank 0.696). Adult patients with smaller LVEDD who received a HeartMate 3 LVAD have comparable clinical outcomes to patients with larger LVEDD. A small left ventricle should not be a contraindication to implantation of this particular durable device in adult patients.

Analysis of hemodynamics and outcomes of pregnant women with congenital heart disease-pulmonary arterial hypertension

Objective: To observe and analysis the changes of hemodynamic parameters and outcomes of pregnant women combined with congenital heart disease-pulmonary arterial hypertension (CHD-PAH). Methods: A prospective analysis of hemodynamic parameters of patients combined with CHD-PAH in Beijing Anzhen Hospital from January 2015 to December 2017 was carried out. Total 99 cases were divided into 4 groups based on systolic pulmonary arterial pressure (SPAP): mild group (SPAP 25-49 mmHg, 1 mmHg=0.133 kPa), moderate group (SPAP 50-79 mmHg), severe group (SPAP≥80 mmHg) and Eisenmenger syndrome group. Results: (1) SPAP of all groups increased during gestation, and the growth rates had no statistical differences (P>0.05). The SPAP in each group decreased after termination but was still higher than the early pregnancy's SPAP. (2) CHD-PAH patients in moderate [2 cm(2) (1-5 cm(2)), 1.0 cm (-2.0 - 2.0 cm)], severe [5 cm(2) (3-9 cm(2)), -3.5 cm (-6.0 - 1.0 cm)] or Eisenmenger syndrome [5 cm(2) (3-6 cm(2)), -1.0 cm (-5.5 - 2.0 cm)] group had larger right atrium area and smaller left ventricular end-diastolic diameter than patients in mild group [1 cm(2) (-1 - 4 cm(2)), 3.0 cm (1.0-6.0 cm)], the differences were statistically significant (all P<0.05). (3) Each group's SPAP/brachial arterial-systolic (BSAP) pressure continously increased during gestation. The SPAP/BSAP only decreased in patients in mild or moderate group after termination. However, the SPAP/BSAP kept rising in patients in severe group or Eisenmenger syndrome group. (4) CHD-PAH patients in severe or Eisenmenger syndrome group had worse cardiac function, in which the rates of Ⅲ-Ⅳ cardiac function were 61%(14/23) and 12/17, compared with patients in mild [8% (2/26)] and moderate [12%(4/33)] group, the differences were statistically significant (all P<0.05). (5) The rates of medicine treatment, cesarean section were higher, the weeks of gestational termination were earlier and the newborn's weights were lower in patients in severe or Eisenmenger syndrome group, the differences were statistically significant (all P<0.05). Conclusions: (1) SPAP keeps rising during gestation in all patients with CHD-PAH, and the SPAP decreases after termination but it's still higher than the early pregnancy's SPAP. This suggests that pregnancy would exacerbate these patients' heart problems, the risk should be fully considered before and during pregnancy. (2) Patients with severe CHD-PAH or combined with Eisenmenger syndrome have lager right atrium area, smaller left ventricular end-diastolic diameter, worse cardiac function, and bigger changes of hemodynamic, the incidence of adverse outcomes of mothers and children is also high, pregnancy should be avoided.

Impact of Pregnancy on Aortic Root in Women with Repaired Conotruncal Anomalies.

The effect of pregnancy on aortic root in women with repaired conotruncal anomalies (CTA) has not been clarified. This study examined aortic diameters during and after pregnancy in women with repaired CTA. A retrospective review of consecutive pregnant women with repaired CTA was performed for results of echocardiography from 1year before pregnancy to 3years after delivery and compared with findings from healthy pregnant volunteers. Participants comprised 42 subjects and 49 deliveries with repaired CTA (CTA group), and 47 healthy pregnant women (control group). Although no maternal aortic events were encountered, aortic diameters during pregnancy increased by 1.0 ± 2.2mm (maximum, 7.0mm) in the CTA group and 0.6 ± 1.3mm (maximum, 3.4mm) in the control group (p = 0.13). The CTA subgroup with increase in aortic diameter ≥ 3.5mm during pregnancy showed no reversion to baseline diameter at follow-up > 6months after delivery. Significant risk factors for increased aortic diameter and no reversal included pulmonary atresia, history of aortopulmonary shunt, older age at repair, and smaller left ventricular end-diastolic diameter pre-pregnancy. Women with repaired CTA tolerated pregnancy and delivery well. However, the aortic root progressively dilated during pregnancy and 1/4 of them, especially those with longstanding high aortic blood flow before repair, showed an increase of aortic root size of ≥ 3.5mm during the peripartum period; this dilatation tended not to revert to the pre-pregnancy diameter. Therefore, serial measurement of the aortic root during pregnancy and after delivery is recommended in these women.

Empagliflozin Attenuates Myocardial Sodium and Calcium Dysregulation and Reverses Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus (DM) has significant effects on cardiac calcium (Ca2+) and sodium (Na+) regulation. Clinical studies have shown that empagliflozin (Jardiance™) has cardiovascular benefits, however the mechanisms have not been fully elucidated. This study aimed to investigate whether empagliflozin modulates cardiac electrical activity as well as Ca2+/Na+ homeostasis in DM cardiomyopathy. Electrocardiography, echocardiography, whole-cell patch-clamp, confocal microscopic examinations, and Western blot, were performed in the ventricular myocytes of control and streptozotocin-induced DM rats, with or without empagliflozin (10 mg/kg for 4 weeks). The results showed that the control and empagliflozin-treated DM rats had smaller left ventricular end-diastolic diameters and shorter QT intervals than the DM rats. In addition, the prolonged action potential duration in the DM rats was attenuated in the empagliflozin-treated DM rats. Moreover, the DM rats had smaller sarcoplasmic reticular Ca2+ contents, intracellular Ca2+ transients, L-type Ca2+, reverse mode Na+-Ca2+exchanger currents, lower protein expressions of sarcoplasmic reticulum ATPase, ryanodine receptor 2 (RyR2), but higher protein expressions of phosphorylated RyR2 at serine 2808 than the control and empagliflozin-treated DM rats. The incidence and frequency of Ca2+ sparks, cytosolic and mitochondrial reactive oxygen species, and late Na+ current and Na+/hydrogen-exchanger currents were greater in the DM rats than in the control and empagliflozin-treated DM rats. Empagliflozin significantly changed Ca2+ regulation, late Na+ and Na+/hydrogen-exchanger currents and electrophysiological characteristics in DM cardiomyopathy, which may contribute to its cardioprotective benefits in DM patients.

The interaction of sex, height, and QRS duration on the effects of cardiac resynchronization therapy on morbidity and mortality: an individual-patient data meta-analysis.

To explore possible associations that may explain the greater benefit from cardiac resynchronization therapy (CRT) reported amongst women. In an individual-patient data meta-analysis of five randomized controlled trials, all-cause mortality and the composite of all-cause mortality or first hospitalization for heart failure (HF) were compared among 794 women and 2702 men assigned to CRT or a control group. Multivariable analyses were performed to assess the impact of sex, QRS duration, HF aetiology, left ventricular end-diastolic diameter (LVEDD), and height on outcome. Women were shorter, had smaller LVEDD, more often left bundle branch block, and less often ischaemic heart disease, but QRS duration was similar between sexes. Women tended to obtain greater benefit from CRT but sex was not an independent predictor of either outcome. For all-cause mortality, QRS duration was the only independent predictor of CRT benefit. For the composite outcome, height and QRS duration, but not sex, were independent predictors of CRT benefit. Further analysis suggested increasing benefit with increasing QRS duration amongst shorter patients, of whom a great proportion were women. In this individual-patient data meta-analysis, CRT benefit was greater in shorter patients, which may explain reports of enhanced CRT benefit among women. Further analyses are required to determine whether recommendations on the QRS threshold for CRT should be adjusted for height. (ClinicalTrials.gov numbers: NCT00170300, NCT00271154, NCT00251251).

Clinical recognition of pure premature ventricular complex-induced cardiomyopathy at presentation

Frequent premature ventricular complexes (PVCs) can induce or worsen left ventricular (LV) systolic dysfunction. The purpose of this study was to identify the clinical pattern of patients having a "pure PVC-induced" cardiomyopathy at presentation. This prospective multicenter study included 155 consecutive patients (age 55 ± 12 years, 96 men [62%], 23% ±12% mean PVC burden) with LV dysfunction and frequent PVCs submitted for ablation and followed up for at least 12 months. Patients with a previously diagnosed structural heart disease (50 [32%]) and those without complete PVC abolition during follow-up who did not normalize LV ejection fraction (LVEF) (24 [15%]) were excluded from the analysis. Of the remaining 81 patients, 41 (51%) had a successful sustained ablation, did not have normalized LVEF, and were classified as having PVC-worsened nonischemic cardiomyopathy, and 40 (49%) who had normalized LVEF were considered as having pure PVC-induced cardiomyopathy. The latter group had higher baseline PVC burden (27% ± 12% vs 12% ± 8%; P <.001), smaller LV end-diastolic diameter (58 ± 5 mm vs 60 ± 6 mm; P = .05), and shorter intrinsic QRS (105 ± 12 vs 129 ± 24 ms; P <.001). Any of the following baseline characteristics accurately identified patients who will not normalize LVEF after PVC ablation (85% sensitivity, 98% specificity): intrinsic QRS >130 ms, baseline PVC burden <17%, and LV end-diastolic diameter >63 mm. Almost half of patients with frequent PVCs and low LVEF of unknown origin normalize LVEF after sustained PVC abolition, and these patients can be identified before ablation.

Outcomes and predictors of recovery in acute-onset cardiomyopathy: A single-center experience of patients undergoing endomyocardial biopsy for new heart failure

About one-third of patients with unexplained acute-onset heart failure (HF) recover left ventricular (LV) function; however, characterization of these patients in the setting of contemporary HF therapies is limited. We aim to describe baseline characteristics and predictors of recovery in patients with acute-onset cardiomyopathy. We previously described 851 patients with unexplained HF undergoing endomyocardial biopsy. In this study, 235 patients with acute-onset HF were further retrospectively examined. Follow-up LV ejection fraction (LVEF) was available for 138 patients. At 1 year, 48 of 138 (33%) had LVEF recovery (follow-up LVEF ≥50%), and 90 of 138 (65%) had incomplete or lack of recovery. Higher cardiac index (P=.019), smaller LV diastolic diameter (P=.002), and lack of an intraventricular conduction delay (IVCD) (P=.002) were associated with LVEF recovery. IVCD (P=.001) and myocarditis (P=.016) were independent predictors of the composite end point of death, LV assist device placement, and/or transplant at 1 year. Those with an IVCD had a significantly lower 1-year survival than those without (P=.007). Patients with a smaller LV end-diastolic diameter, higher cardiac index, and lack of IVCD at presentation for acute-onset HF were more likely to have LVEF recovery. IVCD was a poor prognostic marker in all patients presenting with acute cardiomyopathy.

Prevalence and predictors of left ventricular reverse remodeling in patients with recent onset dilated cardiomyopathy on tailored medical therapy

To observe the frequency and explore the predictors of left ventricular reverse remodeling(LVRR) in patients with recent onset dilated cardiomyopathy(RODCM) on tailored medical therapy. Patients hospitalized with RODCM in Heart Failure Care Unit in Fuwai Hospital from October 2008 to December 2013 were reviewed and followed up to December 2014 or death or cardiac transplantation.Patients were treated with tailored medical therapy. LVRR was defined as an at least 10% increase in left ventricular ejection fraction(LVEF) and to a final level of ≥ 50% and an at least 10 mm decrease in left ventricular end-diastolic diameter(LVEDD) and to a final level of ≤ 55 mm on repeat echocardiogram. Clinical, electrocardiogram and echocardiographic variables at baseline were evaluated to identify predictors of LVRR by multivariable logistic regression analysis. A total of 137 patients with RODCM were enrolled in this analysis. During a median follow-up period of 25 months(range 6 to 64 months) with repeat echocardiography, 46 patients(33.6%) were defined as LVRR, LVEF increased from(30.8±5.9) % at baseline to(59.7±4.6) % on follow-up(P<0.01) and LVEDD decreased from(63.8±4.0) mm at baseline to (49.6±3.5) mm on follow-up(P<0.01) in these patients. Multivariable logistic regression analysis showed that higher systolic blood pressure at presentation(per 10 mmHg(1 mm Hg=0.133 kPa) increase, OR=1.379, P<0.01), shorter QRS interval(≤ 100 ms vs. >100 ms, OR=2.959, P<0.01) and smaller LVEDD(per 5 mm increase, OR=0.684, P<0.01) at baseline were independent predictors of LVRR. On current tailored medical therapy, LVRR could be achieved in about one third of patients with RODCM. Patients with higher systolic blood pressure on admission, shorter QRS interval and smaller LVEDD at baseline are associated with a higher likelihood of occurrence of LVRR.

Role of UTS2 gene in the genetic susceptibility to atrial fibrillation in the Chinese population

ObjectiveAtrial fibrosis plays a key role in the inducibility and persistence of atrial fibrillation. Urotensin II (U-II/UTS2) induces cardiac fibrosis by increasing fibroblast collagen synthesis and increased U-II plasma levels...

HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic Cardiomyopathy.

Peroxisome proliferator-activated receptors (PPARs) regulate cardiac glucose and lipid homeostasis. Histone deacetylase (HDAC) inhibitor has anti-inflammatory effects which may play a key role in modulating PPARs and fatty acid metabolism. The aim of this study was to investigate whether HDAC inhibitor, MPT0E014, can modulate myocardial PPARs, inflammation, and fatty acid metabolism in diabetes mellitus (DM) cardiomyopathy. Electrocardiography, echocardiography, and western blotting were used to evaluate the electrophysiological activity, cardiac structure, fatty acid metabolism, inflammation, and PPAR isoform expressions in the control and streptozotocin-nicotinamide-induced DM rats with or without MPT0E014. Compared to control, DM and MPT0E014-treated DM rats had elevated blood glucose levels and lower body weights. However, MPT0E014-treated DM and control rats had smaller left ventricular end-diastolic diameter and shorter QT interval than DM rats. The control and MPT0E014-treated DM rats had greater cardiac PPAR-α and PPAR-δ protein expressions, but less cardiac PPAR-γ than DM rats. Moreover, control and MPT0E014-treated DM rats had lower concentrations of 5′ adenosine monophosphate-activated protein kinase 2α, PPAR-γ coactivator 1α, phosphorylated acetyl CoA carboxylase, cluster of differentiation 36, diacylglycerol acyltransferase 1 (DGAT1), DGAT2, tumor necrosis factor-α, and interleukin-6 protein than DM rats. HDAC inhibition significantly attenuated DM cardiomyopathy through modulation of cardiac PPARS, fatty acid metabolism, and proinflammatory cytokines.

Abstract 18299: Device Selection: Does Ventricular Size Matter in LVAD Recipients?

Introduction: Axial and centrifugal-flow left ventricular assist devices (LVAD) have varied response to changes in loading conditions. Whether ventricular size modulates the response to LVAD therapy between the axial flow Heartmate II (HMII) and centrifugal flow Heartware (HVAD) is unknown. Hypothesis: Adverse event and survival rates between devices are affected by recipient pre-op left ventricular end-diastolic diameter (LVEDD). Methods: Data on 1,149 continuous-flow LVAD recipients from May 2004 to May 2015 was pooled from the Mechanical Circulatory Support Research Network (MCSRN). The effect of pre-op LVEDD on the instantaneous hazard of death and adverse events was evaluated between HMII (n=864) and HVAD (n=283). Results: The average LVEDD was 7.0cm and did not differ between the device recipients. Patients with a smaller LVEDD (≤ 6.3cm) were more likely female 39% v. 24% (p &lt; 0.0001) and to have an ischemic cardiomyopathy (30% v. 24%, p = 0.045). For every 1cm increase in pre-op LVEDD, the adjusted hazard ratio (HR) for mortality increased with HVAD (HR 1.31, 95% CI 0.94-1.82, p = 0.005) and decreased with HMII (HR 0.78, 95% CI 0.67-0.92, p = 0.005), Figure 1a. Other predictors of mortality included age (HR 1.31, 95% CI 1.12 - 1.53 per 10y, p &lt; 0.001) and bilirubin (HR 1.15, 95% CI 0.94-1.42 per mg/dL, p = 0.027). LVEDD by device type interaction was not a significant predictor of gastrointestinal bleeding or pump thrombosis. The risk of stroke increased with LVEDD for HVAD and decreased for HMII, but this did not reach statistical significance, Figure 1b. Ischemic etiology of heart failure (HR 1.7 95% CI 1.14 - 2.55, p = 0.01) and HVAD device use (HR 1.47 95% CI 1.00 - 2.17, p = 0.03) were significant predictors of stroke. Conclusions: Our data suggest important differences exist in patient outcomes between HMII and HVAD based on pre-op ventricular size. Studies are needed to determine if these differences in outcome are due to device or flow-specific differences in patient support.

(532) - At Left Ventricular Assist Device (LVAD) Implantation, Morphologic Differences Are Observed Between Patients With Improved Cardiac Function Allowing LVAD Removal and Patients With Prolonged LVAD Support as a Bridge to Transplantation

To evaluate differences in morphologic parameters of ventricular remodeling in tissue samples and echocardiograms obtained at left ventricular (LV) assist device (LVAD) implantation in patients who later had sufficient clinical improvement to undergo device explantation versus those who required prolonged continuous-flow (CF) LVAD support and subsequent orthotopic heart transplantation (OHT). We evaluated 25 CF-LVAD patients, 10 of whom had improved cardiac function allowing device removal and 15 of whom underwent long-term device support (>24 months) and subsequent OHT. In all cases, myocardial tissue samples were collected from the LV core obtained at device implantation. Computerized morphometry was used to evaluate fibrosis and hypertrophy, including the cytoplasmic and nuclear diameter. Echocardiographic and hemodynamic parameters at the time of LVAD implantation were correlated with the histopathologic findings. Ten patients (7 men, 3 women; age 30±10 years) had their LVAD (HeartMateII) explanted due to cardiac functional improvement. Fifteen patients (11 men, 4 women; age 46±15 years) underwent OHT after 33±8 months (range: 26-50 months) of CF-LVAD support (HeartMate II, 13 cases; HeartWare, 2 cases). Four patients had ischemic cardiomyopathy, and 11 had nonischemic disease. At LVAD implantation, the LV core from the explant group showed a smaller myocyte diameter (24.55±4.63 vs. 37.09±10.22µ; P=0.0003), a smaller nuclear diameter (12.21±1.72 vs. 15.65±3.88µ; P=0.003), and less fibrosis (10.24±4.03% vs. 17.5±10.36%; P=0.014) than were observed in the transplant group. The left ventricular end-diastolic diameter (LVEDD) was smaller in the explant group than in the transplant group (6.37±0.63 vs. 7.18±1.11 cm; P=0.017). Patients with clinical improvement allowing LVAD explantation had less hypertrophy, less fibrosis, and a smaller LVEDD at the time of LVAD implantation than did patients who required prolonged LVAD support and subsequent OHT. These findings suggest that less extensive morphologic ventricular remodeling changes at LVAD implantation may help determine which subset of patients may have a potential for myocardial reconditioning.

Predictors of positive response to cardiac resynchronization therapy

BackgroundApproximately 30% of patients treated with cardiac resynchronization therapy (CRT) do not achieve favourable response. The purpose of the present study was to identify echocardiographic and clinical predictors of a positive response to CRT.MethodsThe study included 82 consecutive heart failure (HF) patients in New York Heart Association (NYHA) functional class III or IV with left bundle branch block (LBBB), QRS duration ≥ 120 ms and left ventricular ejection fraction (LVEF) ≤ 35%. Statistical analysis was performed using IBM SPSS statistical software (SPSS v.21.0 for Mac OS X). A p value < 0.05 was considered statistically significant.ResultsEchocardiographic response was established in 81.6% and clinical response was achieved in 82.9% of patients. Significant univariate predictors of favourable echocardiographic response after 12 months were smaller left ventricular end-diastolic diameter (LVEDD) (odds ratio [OR] 0.89; 95% confidence interval [CI] 0.82 - 0.97, p = 0.01), and smaller left ventricular end-systolic diameter (LVESD) (OR 0.91; 95% CI 0.85 - 0.98, p = 0.01). Lower uric acid concentration was associated with better echocardiographic response (OR 0.99; 95% CI 0.99 - 1.0, p = 0.01). Non-ischemic HF etiology (OR 4.89; 95% CI 1.39 - 17.15, p = 0.01) independently predicted positive clinical response. Multiple stepwise regression analysis demonstrated that LVEDD lower than 75 mm (OR 5.60; 95% confidence interval [CI] 1.36 - 18.61, p = 0.01) was the strongest independent predictor of favourable echocardiographic response.ConclusionsSmaller left ventricular end-diastolic and end-systolic diameters and lower serum uric acid concentration were associated with better response to CRT. Left ventricular end-diastolic diameter and non-ischemic heart failure etiology were the strongest independent predictors of positive response to CRT.

Frequency and Predictors of Normalization of Left Ventricular Ejection Fraction in Recent-Onset Nonischemic Cardiomyopathy

Emerging evidence has shown the potential of marked improvement in left ventricular ejection fraction (LVEF) in patients with recent-onset cardiomyopathy (ROCM) on medical therapy. This study was designed to determine the frequency and to identify predictors of normalization of LVEF in a cohort of Chinese patients with ROCM receiving contemporary medication. A consecutive series of patients admitted from October 2008 to November 2012 with the clinical diagnosis of ROCM and LVEF ≤ 40% by echocardiography at presentation were followed up at least 12 months to identify those with normalization of LVEF, defined as an increase in LVEF to a final level of ≥ 50%. An array of clinical and echocardiographic variables regarded as potentially relevant to normalization was evaluated to identify predictors using logistic regression analysis. After a mean follow-up of 31 ± 13 months, 48% of 128 patients had normalized their LVEF, showing a significant increase in LVEF from 32 ± 6% to 58 ± 5%, of which 68% occurred within 1 year after initial diagnosis. Multivariate analysis demonstrated that normalization of LVEF was associated with a history of hypertension, higher systolic blood pressure at presentation, shorter electrocardiographic QRS duration, smaller left ventricular end-diastolic diameter, and higher LVEF by echocardiography at baseline. In conclusion, nearly 1/2 of a relatively large number of Chinese patients with ROCM have shown normalization of LVEF on current medical therapy after a medium-term follow-up, which was associated with some clinical and echocardiographic parameters.