Smaller Left Ventricular Dimensions Research Articles

Cardiac structure and function in people with cystic fibrosis

Abstract Background Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organs, however the extent of cardiac involvement in CF is yet to be determined. The remarkable therapeutic advancements with new highly effective CF transmembrane conductance regulator (CFTR) modulator treatment and subsequent increase in life expectancy substantiates further research. Purpose We aimed to explore the prevalence of abnormalities and potential subclinical alterations in cardiac structure and function in adults with CF compared to matched controls and investigate potential cardiovascular risk factors in people with CF (pwCF). Methods In this cross-sectional study, 104 adult pwCF in Denmark underwent clinical and echocardiographic examination. All participants were matched 1:1 with controls from the general population on age and sex. Uni- and multivariable linear regression models with adjustment for heart rate, FEV1, smoking status, hypertension and CF-related diabetes (CFRD) were used to test for differences in echocardiographic parameters between cases and controls. Abnormal cardiac function was defined as left ventricular ejection fraction (LVEF) <50%, left ventricular (LV) global longitudinal strain (GLS) < 16% or presence of diastolic dysfunction. Uni- and multivariable logistic regression models adjusted for age, sex, homozygous genotype, FEV1/FVC, BMI, smoking status, CFRD, pancreatic insufficiency, hypertension, and ischemic heart disease were performed to assess associations between potential risk factors and cardiac dysfunction in CF. Forest plots were constructed to visually represent the findings. Results Of 104 pwCF, 44% were female, mean age was 34 years, 93% received CFTR modulator treatment, and 91% had mutations with only minimal CFTR function (mutation class I-III). The prevalence of abnormal cardiac function in pwCF was 44% versus 22% in controls. Compared to controls, pwCF were found to have smaller LV dimensions, worse LV diastolic function, and more impaired right ventricle (RV) as well as LV systolic function (Table). After multivariable adjustment, LV diastolic function as well as LV and RV systolic function remained impaired in pwCF as compared to controls. Male sex and decreasing FEV1/FVC ratio remained independently associated with abnormal cardiac function in pwCF (male sex: OR 3.94 (1.56; 9.95), p=0.004 and FEV1/FVC ratio: OR 2.05 per 0.1 unit decrease (1.21; 3.52), p=0.008, respectively) (Figure). Conclusion Both left- and right-sided cardiac alterations were found in pwCF. After adjustments for potential risk factors, both RV and LV systolic measures remained altered in pwCF, compared to controls. Male sex and decreasing pulmonary function evaluated by FEV1/FVC-ratio were identified as factors associated with abnormal cardiac function in pwCF.Figure

Beyond the Initial Insult: Clinical Characteristics and Prognosis of Heart Failure with Improved Ejection Fraction

Introduction: Heart failure with improved ejection fraction (HFimpEF) is a recently defined subtype of HF, characterized by an increase in ejection fraction (EF) after a prior diagnosis of reduced EF. There are limited data on the characteristics and outcome of this patient subset. The study aimed to investigate the clinical profile and prognosis of this patient group. Methods: HFimpEF patients from a large echocardiography database with comprehensive clinical and outcome data were evaluated for clinical characteristics and outcomes including mortality and cardiovascular hospitalizations. HFimpEF was defined as prior HF diagnosis with EF ≤40% followed by an EF increase of ≥10% to >40%. Results: The study included 2,883 patients with an EF ≤40%. 27% (777) fulfilled criteria of HFimpEF. Non-ischemic cardiomyopathy, female sex, and smaller left ventricular dimensions were associated with EF improvement. Median follow-up duration was 1,346 days. Patients with HFimpEF had a significantly improved prognosis compared to those without EF improvement. Patients with a significant improvement in the EF (≥50%) experienced a 30% lower mortality rate (HR: 0.70, 95% CI: 0.57–0.86, p < 0.001) and a decreased risk of cardiovascular hospitalizations. Conclusions: HFimpEF is a distinct clinical entity observed in 27% of patients with initially reduced EF and conveys a better prognosis. However, even with improvement, EF in most patients does not fully recover, and clinical events can still occur.

Are there etiology-specific risk factors for adverse outcomes in patients on Impella 5.5 support?

ObjectivesTo identify possible etiology-specific differences in preoperative risk factors for major adverse events during Impella 5.5 support in patients with ischemic (ICM) and nonischemic cardiomyopathy (NICM). MethodsFrom October 2019 to January 2023, 228 Impella 5.5 devices were inserted at our institution. Patients were stratified into ICM (n = 124) and NICM (n = 104) cohorts. The primary outcome was a composite of death/stroke/new-onset dialysis while actively receiving Impella 5.5 support. Random forests identified preoperative factors predictive of the primary outcome separately for each cohort, with ranking by variable importance. ResultsThe primary outcome occurred in 42 (34%) patients with ICM and 35 (34%) patients with NICM. Twenty-one (17%) patients with ICM and 21 (20%) patients with NICM died on Impella 5.5; stroke occurred in 12 (9.7%) patients with ICM and 3 (2.9%) patients with NICM, and new-onset dialysis was initiated in 23 (19%) patients with ICM and 24 (23%) patients with NICM while actively receiving Impella 5.5 support. Risk factors reflecting systemic and myocardial cellular injury, end-organ and cardiopulmonary failure, right ventricular dysfunction, and smaller left ventricular dimensions were most predictive of adverse outcomes in both cohorts. Indications for Impella 5.5 and device strategy (bridge to recovery, advanced therapies, or decision) were not top risk factors in either cohort. ConclusionsRisk factors related to preoperative stability, right ventricular dysfunction, and left ventricular size were more predictive of adverse outcomes while actively receiving Impella 5.5 support than indication or device strategy. These factors could help identify high-risk patients who may benefit from additional tailored management to reduce their risk for these impactful adverse outcomes while on Impella 5.5 support.

Clinical Implication of Supra-Normal Left Ventricular Ejection Fraction in Patients Undergoing Transcatheter Aortic Valve Replacement

Background: Individuals with heart failure displaying supra-normal left ventricular ejection fraction (snLVEF) may exhibit less favorable clinical outcomes in contrast to their counterparts with normal left ventricular ejection fraction (nLVEF). The distinctive characteristics and mid-term prognosis of individuals with severe aortic stenosis and snLVEF following transcatheter aortic valve replacement (TAVR) remain enigmatic. Methods: Among 7393 patients diagnosed with severe aortic stenosis who underwent TAVR between 2013 and 2019 and were enlisted in the optimized transcatheter valvular intervention (OCEAN-TAVI) multicenter registry (UMIN000020423), we selected patients with left ventricular ejection fraction (LVEF) ≥ 50%. snLVEF was defined as LVEF exceeding 65%. We compared the baseline characteristics and assessed three-year post-TAVR mortality and heart failure readmission rates between the snLVEF (LVEF &gt; 65%) and nLVEF cohorts (LVER 50–65%). Results: Our study cohort comprised 5989 patients (mean age 84.4 ± 5.1 years and 1783 males). Among these, 2819 patients were categorized within the snLVEF cohort, while the remaining 3170 were allocated to the nLVEF group. Individuals within the snLVEF cohort were more likely to be female and displayed lower levels of natriuretic peptides, as well as smaller left ventricular dimensions in comparison to their nLVEF counterparts (p &lt; 0.05 for all). The presence of snLVEF emerged as an independent predictor of the three-year composite endpoint relative to nLVEF, with an adjusted hazard ratio of 1.16 (95% confidence interval 1.02–1.31, p = 0.023) after accounting for several potential confounding factors. Conclusions: snLVEF was relatively common among candidates for TAVR with preserved ejection fraction. Patients harboring snLVEF appear to manifest a distinctive clinical profile and encounter less favorable clinical outcomes following TAVR in contrast to those characterized by nLVEF.

Exaggerated myocardial torsion may contribute to dynamic left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

Dynamic left ventricular (LV) outflow tract obstruction (LVOTO) is associated with symptoms and increased risk of developing heart failure in hypertrophic cardiomyopathy (HCM). The association of LVOTO and LV twist mechanics has not been well studied in HCM. The aim of the study was to compare the pattern of LV twist in patients with HCM associated with asymmetrical septal hypertrophy with and without LVOTO. Echocardiography (including speckle tracking) was performed in 212 patients with HCM, divided according to the absence (n = 130) or presence (n = 82) of LVOTO (defined as peak pressure gradient ≥30 mmHg either at rest and/or with Valsalva manoeuvre). Patients with LVOTO were older, had smaller LV dimensions, a higher LV ejection fraction (LVEF), a longer anterior mitral valve leaflet length, and a higher early transmitral pulsed wave to septal tissue Doppler velocity ratio (E/E'). A univariate analysis showed that peak twist was significantly higher in patients with LVOTO compared with patients without LVOTO (19.7 ± 7.3 vs. 15.7 ± 6.0, P = 0.00015). Peak twist was similarly enhanced in patients with LVOTO, manifesting only during Valsalva (19.2 ± 5.6, P = 0.007) and patients with resting LVOTO (19.9 ± 8.0, P = 0.00004) compared with patients without LVOTO (15.7 ± 6.0). A stepwise forward logistic regression analysis showed that LVEF, LV end-systolic dimension indexed to body surface area, anterior mitral valve leaflet length, E/E', and peak twist were all independently associated with LVOTO. This study demonstrates that increased peak LV twist is independently associated with LVOTO in patients with HCM. Peak twist was similarly exaggerated in patients with only latent LVOTO, suggesting that it may play a contributory role to LVOTO in HCM.

Mitral valve prolapse in patients with atrial septal defect: A quantitative three-dimensional echocardiographic analysis.

Mitral valve (MV) prolapse is highly prevalent in patients with atrial septal defect (ASD). Abnormal left ventricular geometry has been proposed as the main mechanism of MV prolapse in ASD, however, the changes in the morphology of the MV apparatus remain to be clarified. Our aim was to assess the MV geometry in patients with ASD and MV prolapse. We evaluated 99 patients (73% female, median age 40 years) with ASD who underwent a three-dimensional transesophageal echocardiogram. Three-dimensional analysis of the MV was done using dedicated automated software. Transthoracic echocardiographic parameters were assessed post ASD closure in 28 patients. MV prolapse was found in 39% of patients. Although smaller left ventricular dimensions and greater interatrial shunt were found in patients with MV prolapse compared with those without prolapse, there was no difference in the subvalvular parameters. MV prolapse was associated with larger mitral anterior-posterior diameter, anterolateral-posteromedial diameter, anterior perimeter, posterior perimeter, total perimeter, and anterior leaflet area (all p<0.05). Mitral regurgitation was more frequent in patients with MV prolapse (80vs. 48%, p=0.002). In patients with ASD, the main mechanism of MV prolapse is the presence of an organic primary process of the MV apparatus (excessive anterior mitral leaflet tissue and mitral annular enlargement).

Missed Opportunities in Identifying Cardiomyopathy Aetiology Prior to Advanced Heart Failure Therapy

Specific aetiologies of cardiomyopathy can significantly impact treatment options as well as appropriateness and prioritisation for advanced heart failure therapies such as ventricular assist device (VAD) or orthotopic heart transplantation (OHT). We reviewed the tissue diagnoses of patients who underwent advanced therapies for heart failure (HF) to identify diagnostic discrepancies. This study presents a retrospective cohort of the aetiology of cardiomyopathy in 118 patients receiving either durable VAD or OHT. Discrepancies between the preoperative aetiological diagnosis of cardiomyopathy with the pathological diagnosis were recorded. Echocardiographic and haemodynamic data were reviewed to examine differences in patients with differing aetiological diagnoses. Twelve (12) of 118 (12/118) (10.2%) had a pathological diagnosis that was discordant with pre-surgical diagnosis. The most common missed diagnoses were infiltrative cardiomyopathy (5) and hypertrophic cardiomyopathy (3). Patients with misidentified aetiology of cardiomyopathy had smaller left ventricular (LV) dimensions on echocardiography than patients with dilated cardiomyopathy (5.8±0.9 vs 6.7±1.1 respectively p=0.01). Most HF patients undergoing VAD and OHT had a correct diagnosis for their heart failure prior to treatment, but a missed diagnosis at time of intervention (VAD or OHT) was not uncommon. Smaller LV dimension on echocardiogram in a patient with a non-ischaemic cardiomyopathy warrants further workup for a more specific aetiology.

Prevalence and Prognostic Importance of Massive Tricuspid Regurgitation in Patients Undergoing Tricuspid Annuloplasty With Concomitant Left-Sided Valve Surgery: A Study on Rheumatic Valvular Heart Disease.

BackgroundThe presence of tricuspid regurgitation (TR) is very common in patients with concomitant left-sided valve disease. Recent studies have advocated an additional grading of massive TR that is beyond severe. The present study sought to characterize the spectrum of TR in patients undergoing tricuspid annuloplasty (TA) and to evaluate the prognostic value of TR severity for post-operative outcome following TA.MethodsA total of 176 patients who underwent TA with combined left-sided valve surgery, secondary to rheumatic valvular heart disease, were prospectively evaluated. The severity of TR was quantified by effective regurgitant orifice area (EROA) using the proximal isovelocity surface area method. Patients were categorized as having non-massive TR (EROA < 0.6 cm2) or massive TR (EROA ≥ 0.6 cm2). Adverse outcome was defined as all-cause mortality or heart failure requiring hospital admission following TA.ResultsA total of 55 (31%) patients were considered to have massive TR. Patients with massive TR had a greater right ventricular dimension but a smaller left ventricular dimension compared with those with non-massive TR. After a median follow-up of 39 months, 35 adverse events occurred. Cox-regression analysis showed that both continuous EROA and dichotomized EROA (massive vs. non-massive TR) were independently associated with adverse events even after multivariable adjustment. Further, Harrell C index demonstrated that the addition of massive TR provided better discrimination ability of a prediction model to known prognosticators following TA.ConclusionsMassive TR is common and up to 31% of study population had massive TR. Massive TR was associated with adverse outcome in patients undergoing TA. Classification of the severity of TR by quantitative measures and identification of massive TR in patients with concomitant left-sided valve disease are essential when considering the optimal timing of corrective surgery.

How to build a successful hypertrophic cardiomyopathy team and ensure training the next generation of myectomy surgeons.

Transaortic extended septal myectomy is the most reliable method for septal reduction for symptomatic patients with obstructive hypertrophic cardiomyopathy. In addition, surgical management of nonobstructive hypertrophic cardiomyopathy is possible for selected patients with diastolic heart failure and small left ventricular end-diastolic cavity dimensions. These procedures, however, are performed infrequently in many centers, and trainees may not be exposed to the preoperative evaluation and intraoperative management of patients with hypertrophic cardiomyopathy. In this paper, we review what we believe are the central features for creating a successful program for septal myectomy and detail our strategies to optimize instruction in these techniques for residents and fellows.

Antihypertrophic Memory After Regression of Exercise-Induced Physiological Myocardial Hypertrophy Is Mediated by the Long Noncoding RNA Mhrt779.

Exercise can induce physiological myocardial hypertrophy (PMH), and former athletes can live 5 to 6 years longer than nonathletic controls, suggesting a benefit after regression of PMH. We previously reported that regression of pathological myocardial hypertrophy has antihypertrophic effects. Accordingly, we hypothesized that antihypertrophic memory exists even after PMH has regressed, increasing myocardial resistance to subsequent pathological hypertrophic stress. C57BL/6 mice were submitted to 21 days of swimming training to develop PMH. After termination of exercise, PMH regressed within 1 week. PMH regression mice (exercise hypertrophic preconditioning [EHP] group) and sedentary mice (control group) then underwent transverse aortic constriction or a sham operation for 4 weeks. Cardiac remodeling and function were evaluated with echocardiography, invasive left ventricular hemodynamic measurement, and histological analysis. LncRNA sequencing, chromatin immunoprecipitation assay, and comprehensive identification of RNA-binding proteins by mass spectrometry and Western blot were used to investigate the role of Mhrt779 involved in the antihypertrophic effect induced by EHP. At 1 and 4 weeks after transverse aortic constriction, the EHP group showed less increase in myocardial hypertrophy and lower expression of the Nppa and Myh7 genes than the sedentary group. At 4 weeks after transverse aortic constriction, EHP mice had less pulmonary congestion, smaller left ventricular dimensions and end-diastolic pressure, and a larger left ventricular ejection fraction and maximum pressure change rate than sedentary mice. Quantitative polymerase chain reaction revealed that the long noncoding myosin heavy chain-associated RNA transcript Mhrt779 was one of the markedly upregulated lncRNAs in the EHP group. Silencing of Mhrt779 attenuated the antihypertrophic effect of EHP in mice with transverse aortic constriction and in cultured cardiomyocytes treated with angiotensin II, and overexpression enhanced the antihypertrophic effect. Using chromatin immunoprecipitation assay and quantitative polymerase chain reaction, we found that EHP increased histone 3 trimethylation (H3K4me3 and H3K36me3) at the a4 promoter of Mhrt779. Comprehensive identification of RNA-binding proteins by mass spectrometry and Western blot showed that Mhrt779 can bind SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (Brg1) to inhibit the activation of the histone deacetylase 2 (Hdac2)/phosphorylated serine/threonine kinase (Akt)/phosphorylated glycogen synthase kinase 3β(p-GSK3β) pathway induced by pressure overload. Myocardial hypertrophy preconditioning evoked by exercise increases resistance to pathological stress via an antihypertrophic effect mediated by a signal pathway of Mhrt779/Brg1/Hdac2/p-Akt/p-GSK3β.

Disproportionate mitral regurgitation: new entity or reflection of measurment errors?

Abstract Funding Acknowledgements Type of funding sources: None. Background The results of recent studies of transcatheter mitral valve repair proposed a new conceptual framework that categorized mitral regurgitation (MR) into proportionate (propMR) or disproportionate (dispropMR) according to the relationship between effective regurgitant orifice area (EROA) and left ventricular (LV) end-diastolic volume (EDV). Purpose To determine the prevalence of dispropMR in consecutive heart failure patients with reduced ejection fraction (HFrEF) undergoing clinically indicated echocardiography over one year period and to examine characteristics of this new entity. Methods We retrospectively identified 179 patients(age:69 ± 12 years, male:132[74%]) with HFrEF who were classified more than mild MR by performing echocardiographer. Following parameters of MR severity were analysed: regurgitant volume(PISA-based regurgitant volume[RVol-PISA] and RVol calculated by the difference of total LV stroke volume by LV planimetry and Doppler-estimated effective LV stroke volume[RVol-SV]), PISA-based EROA and regurgitant fraction (RF). Grading of MR severity based on RVol was performed (mild:&amp;lt;30 ml, mild-moderate:30-44ml, moderate-severe:45-59 ml, severe:≥60 ml). The distinction between propMR and dispropMR was determined by using a proportionality scheme by Grayburn, considering ratio EROA/LVEDV. DispropMR was identified by the ratio greater than 0.14, while the others were classified as propMR. Results In our cohort, 49(27.4%)patients had dispropMR. Both MR groups were comparable in age and gender. DispropMR group had significantly smaller LV dimensions(LV end-diastolic diameter:59 ± 9mm vs. 65 ± 8mm,p &amp;lt; 0.001; LVEDV:164 ± 54ml vs. 222 ± 60ml,p &amp;lt; 0.001) and higher EF(41 ± 11% vs. 34 ± 9%, p &amp;lt; 0.001). Higher proportion of primary MR was noted in dispropMR group(15[31%] vs. 4[3.3%] patients, p &amp;lt; 0.001). Significant differences were observed in PISA-based quantification of MR between both groups (p &amp;lt; 0.001, for all), whereas RVol-SV was comparable(p = 0.667;Figure A). Discrepant grading in MR severity between RVol-PISA and RVol-SV methods was observed(p &amp;lt; 0.001), with significant high discordance in dispropMR(p &amp;lt; 0.001) and no significant differences in propMR(p = 0.187;Figure B). Additionally, difference in RVol assessed by PISA method and SV method were more prominent in dispropMR (RVol difference: dispropMR:27 ml[17-46] vs. propMR:13 ml[-4 to 24],p &amp;lt; 0.001). MR severity would be reclassified in a substantial proportion of dispropMR when considering RVol-SV. Conclusion Our results suggest that dispropMR may be found in roughly one fourth of echocardiographic studies in patients with HFrEF. DispropMR patients have less extensive LV remodelling and more severe MR based on PISA parameters compared to propMR. However, inconsistencies between parameters of MR severity in dispropMR might suggest echocardiographic limitations of quantitative grading of the MR severity or/and LV volume assessment rather than a new pathophysiological concept of disproportionate MR. Abstract Figure A, B

Reduced Biventricular Volumes and Myocardial Dysfunction Long-term After Pediatric Heart Transplantation Assessed by CMR.

Long-term cardiac remodeling after heart transplantation (HT) in children has been insufficiently characterized. The aim of our study was to evaluate ventricular size in HT patients using cardiovascular magnetic resonance (CMR) imaging, to find underlying factors related to potentially abnormal cardiac dimensions and to study its impact on functional class and ventricular function. Seventy-five pediatric HT recipients (age 14.0 ± 4.2 y) were assessed by using CMR 11.2 ± 5.4 years after HT. Right ventricular (RV) and left ventricular (LV) volumes and mass were derived from short-axis cine images and myocardial strain/strain rate was assessed using myocardial feature tracking technique. Results were compared with a healthy reference population (n = 79, age 13.7 ± 3.7 y). LV end-diastolic ventricular volumes were smaller (64 ± 12 versus 84 ± 12 mL/m; P < 0.001) while mass-to-volume ratio (0.86 ± 0.18 versus 0.65 ± 0.11; P < 0.001) and heart rate (92 ± 14 versus 78 ± 13 beats/min; P < 0.001) were higher in HT patients. LV-ejection fraction (EF) was preserved (66% ± 8% versus 64% ± 6%; P = 0.18) but RV-EF (58 ± 7 versus 62% ± 4%, P = 0.004), LV systolic longitudinal strain (-12 ± 6 versus -15% ± 5%; P = 0.05), diastolic strain rate (1.2 ± 0.6 versus 1.5 ± 0.6 1/s; P = 0.03), and intra and interventricular synchrony were lower in the HT group. Smaller LV dimensions were primarily related to longer follow-up time since HT (β = -0.38; P < 0.001) and were associated with worse functional class and impaired ventricular systolic and diastolic performance. Cardiac remodeling after pediatric HT is characterized by reduced biventricular size and increased mass-to-volume ratio. These adverse changes evolve gradually and are associated with impaired functional class and ventricular dysfunction suggesting chronic maladaptive processes affecting allograft health.

MitraClip: How Do We Reconcile the Inconsistent Findings of MITRA-FR and COAPT?

Secondary mitral regurgitation (MR) is a common valvular disorder in patients with left ventricular (LV) dysfunction and is associated with worse morbidity and mortality. New data on percutaneous mitral valve (MV) repair suggest that targeting the valve itself may improve outcomes. Our objective is to review two recent trials (MITRA-FR and COAPT) with regard to percutaneous MV repair. We will dive into their methodology and results and propose potential explanations for their divergent outcomes. MITRA-FR and COAPT studied the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone in patients with secondary MR. COAPT found an overwhelming benefit in reduction in HF hospitalization and mortality whereas MITRA-FR found no difference between treatment groups. Patient selection, differences in procedural outcomes, and smaller LV dimensions may explain these diametrically opposed results. Secondary MR is a common valvular disorder with complex pathophysiology. There are certain patients who will not benefit from percutaneous MV repair. The results of MITRA-FR and COAPT suggest that percutaneous MV repair may benefit carefully selected individuals with secondary MR on maximum tolerated doses of GDMT.

Incidence and predictors of mismatch after mechanical mitral valve replacement.

Background Patient-prosthesis mismatch after mitral valve replacement has an unfavorable postoperative hemodynamic outcome, which underlines the importance of identifying and preventing prosthesis- and patient-related risk factors. This study was conducted to determine the incidence and identify possible predictors of patient-prosthesis mismatch. Methods A prospective study was conducted on 715 patients with a mean age of 42 ± 11 years who underwent mechanical mitral valve replacement between 2013 and 2017. The effective orifice area of the prostheses was estimated by the continuity equation, and a mismatch was defined as an effective orifice area index ≤1.2 cm2·m−2. The mean clinical and echocardiographic follow-up was 26.74 ± 11.58 months. Multivariate regression analysis was performed to identify predictors of patient-prosthesis mismatch. Results Patient-prosthesis mismatch was detected in 382 (53.4%) patients. A small mechanical prosthesis (&lt;27 mm) was inserted in 54.3%. Mortality during follow-up was 9% (65 patients). Patient-prosthesis mismatch was identified in patients with preoperative rheumatic mitral valve pathology, associated tricuspid regurgitation, higher New York Heart Association class, preoperative atrial fibrillation, mitral stenosis, and small preoperative left ventricular dimensions. Multivariate analysis identified mitral stenosis, preoperative atrial fibrillation, and small postoperative left ventricular end-diastolic dimension as risk factors for patient-prosthesis mismatch. Conclusion Patient-prosthesis mismatch is a common sequela after mechanical mitral valve replacement. Identification of predictors of patient-prosthesis mismatch can help so that a preoperative strategy can be implemented to avoid its occurrence.

Predictors of cardiac function in acute heart failure patients with mid-range ejection fraction: AURORA study.

AimThe factors correlated with prognosis in heart failure with mid‐range ejection fraction (HFmrEF) is unclear, especially for acute heart failure (AHF) with HFmrEF. Thus, we investigated the factors correlated with the improvement in the ejection fraction (EF) over 1 year in AHF patients with HFmrEF.Methods and resultsIn Acute Heart Failure Registry in the Osaka Rosai Hospital, we examined 159 consecutive HFmrEF patients out of 1051 HF patients who were admitted to our hospital for AHF from January 2015 to December 2017. We divided them into improved EF (IM) group whose EF improved (≧10%) and non‐IM group who had no improvement. We compared the baseline characteristics, echocardiographic data, medications, examinations for ischaemia, invasive treatments, and clinical outcomes between IM group and non‐IM group. IM group consisted of 21 patients (20%). IM group had a significantly more de novo heart failure, higher serum albumin (Alb), lower EF, smaller left ventricular dimension during diastole, more frequent coronary angiogram during hospitalization, and coronary intervention. Multivariate analysis revealed that Alb, left ventricular dimension during diastole, and coronary angiogram performed during hospitalization were independently associated with the improvement in the EF. In addition, IM group had less rehospitalizations over 1 year and a greater reduction in the B‐type natriuretic peptide level during the follow‐up than non‐IM group.ConclusionsIn AHF patients with HFmrEF, we should evaluate for any ischaemic heart disease during hospitalization, especially in patients with non‐enlarged left ventricular and non‐reduced serum Alb. AHF patients with HFmrEF who showed improvement in the EF tended to have better prognosis than those without improvement.

February 2019 at a glance: pathophysiology, exercise capacity, diuretics and valve disease.

February 2019 at a glance: pathophysiology, exercise capacity, diuretics and valve disease.

Left ventricular reverse remodelling predicts long-term outcomes in patients with functional mitral regurgitation undergoing MitraClip therapy: results from a multicentre registry.

To explore whether left ventricular reverse remodelling (LVRR) is a predictor of outcomes in patients with functional mitral regurgitation (FMR) undergoing MitraClip procedure. We analysed 184 consecutive patients with FMR who underwent successful MitraClip procedure. LVRR was defined as a reduction in left ventricular end-systolic volume ≥ 10% from baseline to 6 months. LVRR was observed in 79 (42.9%) patients. Compared with non-LVRR, LVRR patients were more likely to be females, less likely to have an ischaemic aetiology of mitral regurgitation or a prior (<6 months) heart failure (HF) hospitalization, and had smaller left ventricular dimensions. New York Heart Association class improved from baseline up to 1-year follow-up in both groups. Higher rates of overall survival (87.3% vs. 75.2%, P = 0.039), freedom from HF hospitalization (77.2% vs. 60%, P = 0.020), and freedom from the composite endpoint (cardiovascular mortality or HF hospitalization) (74.7% vs. 55.2%; P = 0.012) were observed in LVRR vs. non-LVRR patients at 2-year follow-up. LVRR was associated with a significant reduction of the adjusted relative risk of mortality, HF hospitalization and composite endpoint [hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.20-0.96, P = 0.040; HR 0.55; 95% CI 0.32-0.97, P = 0.038; and HR 0.54; 95% CI 0.32-0.92, P = 0.023, respectively]. Female gender, absence of diabetes, freedom from prior HF hospitalization, non-ischaemic aetiology of mitral regurgitation, and left ventricular end-diastolic diameter < 75 mm were found to be independent predictors of LVRR. Left ventricular reverse remodelling is associated with better long-term outcomes in patients with FMR successfully treated with MitraClip. A careful patient selection may be useful as specific baseline features predict favourable left ventricular remodelling. [Correction added on 17 January 2019, after online publication: the preceding sentence has been changed.].

Left ventricular end‐diastolic volume predicts exercise capacity in patients with a normal ejection fraction

Exercise capacity is a powerful predictor of all-cause mortality. The duration of exercise with treadmill stress testing is an important prognostic marker in both healthy subjects and patients with cardiovascular disease. Left ventricular (LV) structure is known to adapt to sustained changes in level of physical activity. Poor exercise capacity in patients with a preserved LV ejection fraction (LVEF) should be reflected in smaller LV dimensions, and a normal exercise capacity should be associated with larger LV dimensions, irrespective of comorbidities. This hypothesis was first tested in a cross-sectional analysis of 201 patients with normal chamber dimensions and preserved LVEF who underwent a clinically indicated treadmill stress echocardiogram using the Bruce protocol (derivation cohort). The best LV dimensional predictor of exercise capacity was then tested in 1285 patients who had a Bruce-protocol treadmill exercise stress test and a separate transthoracic echocardiogram (validation cohort). In the derivation cohort, there was a strong positive relationship between exercise duration and LV end-diastolic volume deciles (r 2 = 0.85; P < 0.001). Regression analyses of several LV dimensional parameters revealed that the body surface area-based LV end-diastolic volume index was best suited to predict exercise capacity (P < 0.0001). In a large validation cohort, LV end-diastolic volume was confirmed to predict exercise capacity (P < 0.0001). Among patients referred for outpatient stress echocardiography who have a preserved LVEF and no evidence of myocardial ischemia, we found a strong positive association between LV volume and exercise capacity.

Relation between electrical and mechanical dyssynchrony in patients with left bundle branch block: An electro- and vectorcardiographic study.

Current guidelines select patients for cardiac resynchronization therapy (CRT) mainly on electrocardiographic parameters like QRS duration and left bundle branch block (LBBB). However, among those LBBB patients, heterogeneity in mechanical dyssynchrony occurs and might be a reason for nonresponse to CRT. This study assesses the relation between electrocardiographic characteristics and presence of mechanical dyssynchrony among LBBB patients. The study included patients with true LBBB (including mid-QRS notching) on standard 12-lead electrocardiograms. Left bundle branch block-induced mechanical dyssynchrony was assessed by the presence of septal flash on two-dimensional echocardiography. Previously reported electro- and vectorcardiographic dyssynchrony markers were analyzed: global QRS duration (QRSDLBBB ), left ventricular activation time (QRSDLVAT ), time to intrinsicoid deflection (QRSDID ), and vectorcardiographic QRS areas in the 3D vector loop (QRSA3D ). The study enrolled 545 LBBB patients. Septal flash (SF) is present in 52% of patients presenting with true LBBB. Patients with SF are more frequent female, have less ischemic heart disease and smaller left ventricular dimensions. In multivariate analysis longer QRSDLBBB , QRSDLVAT and larger QRSA3D were independently associated with SF. Of all parameters, QRSA3D has the best accuracy to predict SF, although overall accuracy remains moderate (59% sensitivity, 58% specificity). The predictive value of QRSA3D remained constant in both sexes, irrespective of ischemic heart disease, ejection fraction and even when categorizing for QRSDLBBB . In LBBB patients, large QRS areas correlate better with mechanical dyssynchrony compared to wide QRSD intervals. However, the overall accuracy to predict mechanical dyssynchrony by electrocardiographic dyssynchrony markers, even when using complex vectorcardiographic parameters, remains low.

Prenatal Mechanistic Target of Rapamycin Complex 1 (m TORC1) Inhibition by Rapamycin Treatment of Pregnant Mice Causes Intrauterine Growth Restriction and Alters Postnatal Cardiac Growth, Morphology, and Function.

BackgroundFetal growth impacts cardiovascular health throughout postnatal life in humans. Various animal models of intrauterine growth restriction exhibit reduced heart size at birth, which negatively influences cardiac function in adulthood. The mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient and growth factor availability with cell growth, thereby regulating organ size. This study aimed at elucidating a possible involvement of mTORC1 in intrauterine growth restriction and prenatal heart growth.Methods and ResultsWe inhibited mTORC1 in fetal mice by rapamycin treatment of pregnant dams in late gestation. Prenatal rapamycin treatment reduces mTORC1 activity in various organs at birth, which is fully restored by postnatal day 3. Rapamycin‐treated neonates exhibit a 16% reduction in body weight compared with vehicle‐treated controls. Heart weight decreases by 35%, resulting in a significantly reduced heart weight/body weight ratio, smaller left ventricular dimensions, and reduced cardiac output in rapamycin‐ versus vehicle‐treated mice at birth. Although proliferation rates in neonatal rapamycin‐treated hearts are unaffected, cardiomyocyte size is reduced, and apoptosis increased compared with vehicle‐treated neonates. Rapamycin‐treated mice exhibit postnatal catch‐up growth, but body weight and left ventricular mass remain reduced in adulthood. Prenatal mTORC1 inhibition causes a reduction in cardiomyocyte number in adult hearts compared with controls, which is partially compensated for by an increased cardiomyocyte volume, resulting in normal cardiac function without maladaptive left ventricular remodeling.ConclusionsPrenatal rapamycin treatment of pregnant dams represents a new mouse model of intrauterine growth restriction and identifies an important role of mTORC1 in perinatal cardiac growth.