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Aims Myocardial work (manually controlled software) and integral-derived longitudinal strain (automatic quantification of strain curves) are two promising tools to quantify dyssynchrony and potentially select the patients that are most likely to have a reverse remodelling due to cardiac resynchronization therapy (CRT). We sought to test and compare the value of these two methods in the prediction of CRT-response. Materials and results Two hundred and forty-three patients undergoing CRT-implantation from three European referral centres were considered. The characteristics from the six-segment of the four-chamber view were computed to obtain regional myocardial work and the automatically generated integrals of strain. The characteristics were studied in mono-parametric and multiparametric evaluations to predict CRT-induced 6-month reverse remodelling. For each characteristic, the performance to estimate the CRT response was determined with the receiver operating characteristic (ROC) curve and the difference between the performances was statistically evaluated. The best area under the curve (AUC) when only one characteristic used was obtained for a myocardial work (AUC = 0.73) and the ROC curve was significantly better than the others. The best AUC for the integrals was 0.63, and the ROC curve was not significantly greater than the others. However, with the best combination of works and integrals, the ROC curves were not significantly different and the AUCs were 0.77 and 0.72. Conclusion Myocardial work used in a mono-parametric estimation of the CRT-response has better performance compared to other methods. However, in a multiparametric application such as what could be done in a machine-learning approach, the two methods provide similar results. [ABSTRACT FROM AUTHOR]

Objective: To assess the mid-term clinical outcomes, hemodynamics, left ventricular (LV) mass regression, and structural valve deterioration (SVD) in patients implanted with the Perceval aortic sutureless valve across valve sizes., Methods: Data were obtained from a multicenter European trial and a US Investigational Device Exemption trial. Echocardiography data were analyzed by an echocardiography core lab. A mixed-effects regression model was used to assess relationships between hemodynamic outcomes, time from the procedure, and valve sizes. The Valve Academic Research Consortium (VARC)-3 definition for bioprosthetic valve failure was applied., Results: A Perceval sutureless valve was implanted in 970 patients. The median patient age was 77.8 years, 57.2% were female, the median Society of Thoracic Surgeons predicated risk of mortality was 3.3% (range, 2.1%-6.2%), and 33.4% had a concomitant procedure. The median clinical follow-up was 45.7 months (range, 28.2-76.1 months). Small and medium valves were implanted more commonly in women than in men (16.9% vs 1.9% for small and 55.1% vs 19.5% for medium; P < .001). The mean aortic valve gradients decreased significantly postimplantation and remained stable across all valve sizes throughout the follow-up period. All patients were free from severe patient-prosthesis mismatch (with an effective orifice area/m 2 of >0.8). Significant LV mass regression was documented regardless valve sizes, plateaued at -9.1% at 5 years. Freedom from SVD and reintervention were 95.2% and 96.3%, respectively, at 5 years and were independent of implanted valve size (P = .22). The VARC-3 stage 3 bioprosthetic valve failure rate was low, 2.8% at 5 years., Conclusions: The Perceval valve demonstrated low and stable mean gradients, significant LV mass regression, and low SVD and reintervention rates across all valve sizes., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. TRIM63 has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in TRIM63 and the development of HCM.Methods: TRIM63 was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls.Results: Sixteen index cases with rare homozygous or compound heterozygous variants in TRIM63 (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15-69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%).Conclusion: TRIM63 appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction. [ABSTRACT FROM AUTHOR]

View large Download slide View large Download slide Systolic heart failure is frequently accompanied by a relevant functional mitral valve regurgitation (FMR) which develops as a direct sequela of the ongoing left ventricular remodelling. The severity of mitral regurgitation is further aggravated by progressive left ventricular enlargement causing leaflet tethering and reduced systolic leaflet movement. The prognosis of such patients is obviously limited by an underlying left ventricular disease, and the correction of secondary FMR has been previously suggested as predominantly 'cosmetic' surgery in the setting of ongoing cardiomyopathy. Inferior results of an isolated annuloplasty in type IIIb FMR supported the philosophy of malignant course of progressive cardiomyopathy and resulted in increasingly restricted indications for mitral valve surgery for FMR in the guidelines. The lack of a standardized pathophysiological approach to correct type IIIb FMR led to the development of valve replacement strategy and edge-to-edge catheter-based mitral valve procedures, which became the most frequent procedures in the FMR setting in Europe. Modern mitral valve surgery combines the advantages of 3-dimensional endoscopic minimally invasive surgical approach with standardized subannular repair to address the pathophysiological background of type IIIb FMR. The perioperative results have been significantly improved, and there is a growing evidence of improved long-term stability of subannular repair procedures as compared to isolated annuloplasty. This review article aims to present the current state-of-the-art of the modern mitral valve surgery in FMR and provides suggestions for future trials analysing the potential advantages in these patients. [ABSTRACT FROM AUTHOR]

There are data showing race-related differences regarding left ventricular (LV) geometry in hypertensive patients. Several authors reported that concentric remodeling is the most common remodeling pattern in hypertensive African-Americans, and this pattern may be related to prognosis. There is little information about the LV remodeling patterns in hypertensive Africans that migrated to Europe, which might have different distributions from those seen in African-Americans. The aim our study was to describe the prevalence of LV remodeling patterns in hypertensive African-Europeans and to compare it with that of hypertensive Caucasians. This is a descriptive study that included 135 consecutive treated hypertensive African-Europeans and 128 hypertensive Caucasians. Patients were examined by transthoracic echocardiography and categorized into the four classic geometric patterns according to LV mass index (LVMi) and relative wall thickness (RWT). The mean age and gender distribution were similar in the 2 groups. Caucasians had significantly higher body mass index, LV diastolic and systolic diameters, while African-Europeans had higher RWT and interventricular septum thickness. No differences in LVMi was found. In the African-European group, the prevalence of normal pattern, concentric remodeling, concentric hypertrophy and eccentric hypertrophy were 13%, 36%, 45% and 6% respectively, while in Caucasians they were 21%, 33%, 34% and 12%, respectively. African-Europeans had a higher prevalence of concentric remodeling and hypertrophy compared to Caucasians (81% vs. 67%, p =.005). This study shows important differences in LV geometry between treated African-European and Caucasian hypertensive patients. Also, African-Europeans may have slightly different characteristics compared to African-Americans. • The differences of geometric left ventricular patterns according to race could be curious. • The left ventricular remodeling patterns in hypertensive African-Europeans are unknown. • Caucasians showed more prevalence of obesity, diabetes and dyslipidaemia. • African-Europeans had higher prevalence of concentric remodeling and hypertrophy. • These differences could clarify the race differences related to adverse outcomes. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to evaluate the association of baseline tricuspid regurgitation (TR) on the outcomes after percutaneous mitral valve repair (PMVR) with the MitraClip system. Methods and results Data from 146 consecutive patients with functional mitral regurgitation (MR) were obtained. Two different groups, dichotomized according to the degree of pre-procedural TR (moderate/severe, n = 47 and none/mild, n = 99), had their clinical and echocardiographic outcomes through 12-month compared. At 30-day, the primary safety endpoint was significantly higher in moderate/severe TR compared with none/mild TR (10.6 vs. 2.0%, P = 0.035). Marked reduction in MR grades observed post-procedure were maintained through 12 months. Although NYHA functional class significantly improved in both groups compared with baseline, it was impaired in moderate/severe TR compared with the none/mild TRgroup (NYHA > II at 30 day: 33.3 vs. 9.2%, P < 0.001; at 1 year: 38.5 vs. 12.3%, respectively, P = 0.006). Left ventricle reverse remodelling and ejection fraction improvement were revealed in both groups. The primary efficacy endpoint at 12-month determined by freedom from death, surgery for mitral valve dysfunction, or grade ≥3+ MR was comparable between groups, but combined death and re-hospitalization for heart failure rates were higher in the moderate/severe TR group. Multivariable Cox regression analysis demonstrated that baseline moderate/severe TR and chronic kidney disease were independent predictors of this combined endpoint. Conclusions Although PMVR with MitraClip led to improvement in MR, TR, and NYHA functional class in patients with baseline moderate/severe TR, the primary safety endpoint at 30-day was impaired, while moderate/severe TR independently predicted death and rehospitalization for heart failure at 12-month. [ABSTRACT FROM AUTHOR]

Surgical ventricular remodeling (SVR) is an invasive method of treating patients with heart failure who also have ischemic cardiomyopathy and reduced ejection fraction (EF). Introduced in the mid-1980s, this technique was met with varying success and relatively high morbidity and mortality despite its theoretical benefits. The development of the BioVentrix Revivent TC System (BioVentrix, Inc., San Ramon, CA) as a less-invasive method of surgical ventricular remodeling has created a novel, multidisciplinary approach to heart failure management, which necessitates multiple subspecialties. Currently in the trial phase in the United States and widely used in Europe, the positive results to date appear promising for the rapid adoption of this procedure. For the cardiac anesthesiologist, a thorough understanding of the patient population, procedural goals, and intraoperative management is essential. This overview discusses the advancement in surgical ventricular remodeling, the pertinent surgical steps of the BioVentrix Revivent TC System placement, and specific anesthetic considerations for this novel procedure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A index of non-invasive myocardial work (MWI) can account for pressure during the assessment of cardiac function, potentially separating the influence of loading conditions from the influence of the underlying tissue remodelling. The aim is to assess LV function accounted for loading and explore hypertensive MWI distribution by comparing healthy individuals to hypertensive patients without and with localized basal septal hypertrophy (BSH). An echocardiogram was performed in 170 hypertensive patients and 20 healthy individuals. BSH was defined by a basal-to-mid septal wall thickness ratio ≥ 1.4. LV speckle-tracking was performed, and the MWI calculated globally and regionally for the apical, mid and basal regions. An apex-to-base gradient, seen in regional strain values, was preserved in the distribution of myocardial work, with the apical region compensating for the impairment of the basal segments. This functional redistribution was further pronounced in patients with localized BSH. In these patients, segmental MWI analysis revealed underlying impairment of regional work unrelated to acute loading conditions. Non-invasive MWI analysis offers the possibility to compare LV function regardless of blood pressure at the time of observation. Changes in MWI distribution can be seen in hypertension unrelated to the load-dependency of strain. Accentuated functional changes affirm the role of BSH as an echocardiographic marker in hypertension.

Background: Truncating variants in the TTN gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers., Methods: Five hundred thirty-seven individuals (61% men; 317 probands) with TTNtv were recruited in 14 centers (372 [69%] with baseline left ventricular systolic dysfunction [LVSD]). Baseline and longitudinal clinical data were obtained. The primary end point was a composite of malignant ventricular arrhythmia and end-stage heart failure. The secondary end point was left ventricular reverse remodeling (left ventricular ejection fraction increase by ≥10% or normalization to ≥50%)., Results: Median follow-up was 49 (18-105) months. Men developed LVSD more frequently and earlier than women (45±14 versus 49±16 years, respectively; P =0.04). By final evaluation, 31%, 45%, and 56% had atrial fibrillation, frequent ventricular ectopy, and nonsustained ventricular tachycardia, respectively. Seventy-six (14.2%) individuals reached the primary end point (52 [68%] end-stage heart failure events, 24 [32%] malignant ventricular arrhythmia events). Malignant ventricular arrhythmia end points most commonly occurred in patients with severe LVSD. Male sex (hazard ratio, 1.89 [95% CI, 1.04-3.44]; P =0.04) and left ventricular ejection fraction (per 10% decrement from left ventricular ejection fraction, 50%; hazard ratio, 1.63 [95% CI, 1.30-2.04]; P <0.001) were independent predictors of the primary end point. Two hundred seven of 300 (69%) patients with LVSD had evidence of left ventricular reverse remodeling. In a subgroup of 29 of 74 (39%) patients with initial left ventricular reverse remodeling, there was a subsequent left ventricular ejection fraction decrement. TTNtv location was not associated with statistically significant differences in baseline clinical characteristics, left ventricular reverse remodeling, or outcomes on multivariable analysis ( P =0.07)., Conclusions: TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD. Male sex and LVSD are independent predictors of outcomes. Mutation location does not impact clinical phenotype or outcomes.

Objective: Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. TRIM63 has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in TRIM63 and the development of HCM., Methods: TRIM63 was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls., Results: Sixteen index cases with rare homozygous or compound heterozygous variants in TRIM63 (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15-69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%)., Conclusion: TRIM63 appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction., Competing Interests: Competing interests: JS-M, JPO, IG-D, IJC-R, MNC, DG-G, AL, LS and MO-G are employees of Health in Code SL. LM is a stakeholder and CEO of Health in Code SL., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Accelerated tPA (tissue-type plasminogen activator) dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis improve short-term computed tomographic-measured right ventricular (RV)-to-left ventricular diameter ratio in massive and submassive pulmonary embolism. The impact on RV remodeling, functional status, and quality of life over the long-term remains unclear., Methods: To study 1-year changes in RV remodeling, functional status, and quality of life, we assessed patients with acute submassive pulmonary embolism randomly assigned to 1 of 4 tPA dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis in the OPTALYSE-PE trial (Optimum Duration and Dose of r-tPA With the Acoustic Pulse Thrombolysis Procedure for Intermediate-Risk Pulmonary Embolism; 8 mg/2 hours, 8 mg/4 hours, 12 mg/6 hours, and 24 mg/6 hours). Echocardiographic assessment included RV-to-left ventricular diameter ratio within 4 hours of treatment end, and at 48 hours, 30 days, 90 days, and 1 year. Functional status was assessed by 6-minute walk test at 30 days, 90 days, and 1 year and PROMIS-PF-6b scores at 30 days, 90 days, 180 days, 270 days, and 1 year. Quality of life was evaluated by PEmb-QOL scores at 30 days, 90 days, 180 days, 270 days, and 1 year., Results: Mean RV-to-left ventricular diameter ratio decreased from baseline to 4 hours and further at 48 hours and 30 days, with reductions maintained at 90 days and 1 year in all groups. Mean 6-minute walk distance, PROMIS-PF-6b, and PEmb-QOL scores improved over the course of 1 year in all groups., Conclusions: Accelerated lower-dose tPA regimens for ultrasound-facilitated, catheter-directed fibrinolysis resulted in sustained recovery of RV-to-left ventricular diameter ratio and tricuspid annular plane systolic excursion and improvements in functional status and quality of life over 1 year. Registration: URL: https://www.ClinicalTrials.gov. Unique Identifier: NCT02396758.

Objectives: This study aimed to investigate the accuracy of a broad range of echocardiographic variables to develop multiparametric scores to diagnose CA in patients with proven light chain (AL) amyloidosis or those with increased heart wall thickness who had amyloid was suspected. We also aimed to further characterize the structural and functional changes associated with amyloid infiltration., Background: Cardiac amyloidosis (CA) is a serious but increasingly treatable cause of heart failure. Diagnosis is challenging and frequently unclear at echocardiography, which remains the most often used imaging tool., Methods: We studied 1,187 consecutive patients evaluated at 3 referral centers for CA and analyzed morphological, functional, and strain-derived echocardiogram parameters with the aim of developing a score-based diagnostic algorithm. Cardiac amyloid burden was quantified by using extracellular volume measurements at cardiac magnetic resonance., Results: A total of 332 patients were diagnosed with AL amyloidosis and 339 patients with transthyretin CA. Concentric remodeling and strain-derived parameters displayed the best diagnostic performance. A multivariable logistic regression model incorporating relative wall thickness, E wave/e' wave ratio, longitudinal strain, and tricuspid annular plane systolic excursion had the greatest diagnostic performance in AL amyloidosis (area under the curve: 0.90; 95% confidence interval: 0.87 to 0.92), whereas the addition of septal apical-to-base ratio yielded the best diagnostic accuracy in the increased heart wall thickness group (area under the curve: 0.80; 95% confidence interval: 0.85 to 0.90)., Conclusions: Specific functional and structural parameters characterize different burdens of CA deposition with different diagnostic performances and enable the definition of 2 scores that are sensitive and specific tools with which diagnose or exclude CA., (Copyright © 2020. Published by Elsevier Inc.)

Despite promising experimental studies and encouraging proof-of-concept clinical trials, interventions aimed at limiting infarct size have failed to improve clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Our objective was to examine whether variables (cardiovascular risk factors, comorbidities, post-procedural variables, cotreatments) might be associated with clinical outcomes in STEMI patients independently from infarct size reduction. The present study was based on a post hoc analysis of the CIRCUS trial database (Clinicaltrials.gov NCT01502774) that assessed the clinical benefit of a single intravenous bolus of cyclosporine in 969 patients with anterior STEMI. Since cyclosporine had no detectable effect on clinical outcomes as well as on any measured variable, we here considered the whole study population as one group. Multivariate analysis was performed to address the respective weight of infarct size and variables in clinical outcomes. Multivariate analysis revealed that several variables (including gender, hypertension, renal dysfunction, TIMI flow grade post-PCI < 3, and treatment administered after PCI with betablockers and angiotensin-converting enzyme inhibitors) had per se a significant influence on the occurrence of [death or hospitalization for heart failure] at 1 year. The relative weight of infarct size and variables on the composite endpoint of [death or hospitalization for heart failure] at 1 year was 18% and 82%, respectively. Several variables contribute strongly to the clinical outcomes of STEMI patients suggesting that cardioprotective strategy might not only focus on infarct size reduction.

Objectives: The authors sought to assess the intermediate-term effects of percutaneous placed valves in the branch pulmonary artery (PA) position., Background: Most patients with large right ventricular outflow tracts (RVOTs) are excluded from available percutaneous pulmonary valve options. In some of these patients, percutaneous branch PA valve implantation may be feasible. The longer-term effects of valves in the branch PA position is unknown., Methods: Retrospective data were collected on patients with significant pulmonary regurgitation who had a percutaneous branch PA valve attempted., Results: Percutaneous branch PA valve implantation was attempted in 34 patients (18 bilateral and 16 unilateral). One-half of the patients were in New York Heart Association (NHYA) functional class III or IV pre-implantation. There were 2 failed attempts and 6 procedural complications. At follow-up, only 1 patient had more than mild valvar regurgitation. The right ventricular end-diastolic volume index decreased from 147 (range: 103 to 478) ml/m 2 to 101 (range: 76 to 429) ml/m 2 , p < 0.01 (n = 16), and the right ventricular end-systolic volume index decreased from 88.5 (range: 41 to 387) ml/m 2 to 55.5 (range: 40.2 to 347) ml/m 2 , p < 0.01 (n = 13). There were 5 late deaths. At a median follow-up of 2 years, all other patients were in NYHA functional class I or II., Conclusions: Percutaneous branch PA valve implantation results in a reduction in right ventricular volume with clinical benefit in the intermediate term. Until percutaneous valve technology for large RVOTs is refined and more widely available, branch PA valve implantation remains an option for select patients., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: This prospective, non-randomised, observational study conducted in Europe was designed in order to assess the long-term safety and efficacy of the Parachute device in ischaemic heart failure subjects as a result of left ventricle remodelling after anterior wall myocardial infarction., Methods and Results: One hundred subjects with New York Heart Association Class II-IV ischaemic heart failure (HF), ejection fraction (EF) between 15% and 40%, and dilated akinetic or dyskinetic anterior-apical wall without the need to be revascularised were enrolled. The primary safety endpoint was procedural- or device-related major adverse cardiac cerebral events (MACCE). The secondary safety endpoint was the composite of mortality and morbidity. Secondary efficacy endpoints included haemodynamic measurements determined by echocardiography, LV volume indices, and assessment of functional improvement measured by a standardised six-minute walk test. Of the 100 subjects enrolled, device implantation was successful in 97 (97%) subjects. The one-year rates of the primary and secondary safety endpoints were 7% and 32.3%, respectively. The secondary endpoints, LV volume reduction (p<0.0001) and six-minute walk distance improvement (p<0.01), were achieved., Conclusions: The favourable outcomes observed in this high-risk population provide reassuring safety and efficacy data to support adoption of this technology as a therapeutic option for HF subjects.

Background: Cardiac resynchronization therapy results in improved ejection fraction in patients with heart failure. We sought to determine whether these effects were mediated by changes in contractility, afterload, or volumes., Methods and Results: In 610 patients with New York Heart Association class I/II heart failure from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study, we performed detailed quantitative echocardiography assessment prior to and following cardiac resynchronization therapy. We derived measures of contractility (the slope [end-systolic elastance] and the volume intercept of the end-systolic pressure-volume relationship, stroke work, and preload recruitable stroke work), measures of arterial load and ventricular-arterial coupling, and measures of chamber size (volume intercept, end-systolic and end-diastolic volumes). At 6 and 12 months, cardiac resynchronization therapy was associated with a reduction in the volume intercept and end-systolic and end-diastolic volumes (P<0.01). There were no consistent effects on end-systolic elastance, stroke work, preload recruitable stroke work, or ventricular-arterial coupling. In the active cardiac resynchronization therapy population, baseline measures of arterial load were associated with the clinical composite score (odds ratio 1.30, 95% CI 1.04 to 1.63, P=0.02). The volume intercept was associated with mortality (hazard ratio 1.90, 95% CI 1.01 to 3.59, P=0.047) and more modestly with the combined end point of mortality or heart failure hospitalization (hazard ratio 1.48, 95% CI 0.8 to 2.25, P=0.06). In contrast, end-systolic elastance, stroke work, preload recruitable stroke work, and ventricular-arterial coupling were not associated with any outcomes., Conclusion: In patients with NYHA Class I/II heart failure, cardiac resynchronization therapy exerts favorable changes in left ventricular end-systolic and end-diastolic volumes and the volume intercept. The volume intercept may be useful to gain insight into prognosis in heart failure., Clinical Trial Registration: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00271154., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous etiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodeling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous etiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodeling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of transcatheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: DOPPLER-CIP aims to determine the optimal noninvasive parameters (myocardial function, perfusion, ventricular blood flow, cell integrity) and methodology (ergometry, echocardiography, scintigraphy, MRI) in a given ischemic substrate that best predicts the impact of an intervention (or the lack thereof) on adverse morphological ventricular remodeling and functional recovery. Moreover, the relative predictive value of each of these parameters, in respect to the cost of extracting this information in order to enable optimization of cost-effectiveness for improved health care, will be determined by this project., Design: DOPPLER-CIP is a multi-center registry study. All patients with ischemic heart disease included in this study undergo at least two noninvasive stress imaging examinations at baseline. The presence/or absence of left ventricular (LV) remodeling will be assessed after a follow-up of 2 years, during which all cardiac events will be registered., Results: 676 patients were included. Currently, baseline data analysis is almost finished and the follow-up is ongoing., Conclusions: After completion, DOPPLER-CIP will provide evidence-based guidelines toward the most effective use of cardiac imaging in the chronically ischemic heart disease patient. The study will generate information, knowledge, and insight into the new imaging methodologies and into the pathophysiology of chronic ischemic heart disease.

Individuals of Indian Asian ethnicity living in the U.K. have at least a 50% excess of cardiovascular disease (CVD) mortality compared with European whites, yet there are no validated tools capable of identifying this excess risk. Left ventricular hypertrophy (LVH) is a powerful prognosticator for future CVD events but its prevalence in Indian Asians is unknown. We examined the prevalence of LVH and the degree of concentric remodeling amongst healthy U.K. Indian Asians compared with European whites recruited to the LOLIPOP (London Life Sciences Prospective Population) study. Transthoracic echocardiography was performed in 2127 subjects aged 35-75 years without history of clinical CVD events. The prevalence of LVH was defined and relative wall thickness was calculated to provide a measure of concentric remodeling. The prevalence of LVH was significantly higher amongst Indian Asian men as compared with European white men, with an unadjusted odds ratio (OR) of 1.8 (95% CI: 1.4-2.6). Following adjustment for clinical and hemodynamic variables, the magnitude of this effect increased (OR 2.8, 95% CI: 1.9-4.2). The degree of concentric remodeling was higher amongst Indian Asians as compared with European whites (adjusted relative wall thickness for men: 0.41 vs. 0.39, P<0.001; women: 0.40 vs. 0.38, P<0.01). An almost threefold higher prevalence of LVH amongst Indian Asian men and a greater degree of concentric remodeling amongst Indian Asian men and women was evident. Investigation of the mechanisms underlying the pathogenesis of LV remodeling and blood pressure etiology may help redress the excess CVD mortality observed in Indian Asians.

Background: Mildly symptomatic heart failure (HF) patients derive substantial clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) as shown in MADIT-CRT. The presence of QRS axis deviation may influence response to CRT-D. The objective of this study was to determine whether QRS axis deviation will be associated with differential benefit from CRT-D., Methods: Baseline electrocardiograms of 1,820 patients from MADIT-CRT were evaluated for left axis deviation (LAD: quantitative QRS axis -30 to -90) or right axis deviation (RAD: QRS axis 90-180) in left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific interventricular conduction delay QRS morphologies. The primary endpoints were the first occurrence of a HF event or death and the separate occurrence of all-cause mortality as in MADIT-CRT., Results: Among LBBB patients, those with LAD had a higher risk of primary events at 2 years than non-LAD patients (20% vs 16%; P = 0.024). The same was observed among RBBB patients (20% vs 10%; P = 0.05) but not in IVCD patients (22% vs 23%; P = NS). RAD did not convey any increased risk of the primary combined endpoint in any QRS morphology subgroup. When analyzing the benefit of CRT-D in the non-LBBB subgroups, there was no significant difference in hazard ratios for CRT-D versus ICD for either LAD or RAD. However, LBBB patients without LAD showed a trend toward greater benefit from CRT therapy than LBBB patients with LAD (HR for no LAD: 0.37, 95% CI: 0.26-0.53 and with LAD: 0.54, 95% CI: 0.36-0.79; P value for interaction = 0.18)., Conclusions: LAD in non-LBBB patients (RBBB or IVCD) is not associated with an increased benefit from CRT. In LBBB patients, those without LAD seem to benefit more from CRT-D than those with LAD., (© 2012 Wiley Periodicals, Inc.)

Objectives: The aim of this study was to evaluate the evolution in Q-wave expression during the first 5 years after a primary, successfully reperfused ST-segment elevation myocardial infarction (MI), using cardiac magnetic resonance (CMR) for infarct location, and to depict changes in infarct size and left ventricular remodeling over time., Background: In the absence of QRS confounders, abnormal Q waves are usually diagnostic of myocardial necrosis. It is hypothesized that Q-wave regression after MI could be related to smaller infarct sizes. Late gadolinium enhancement accurately depicts MI of any age., Methods: Forty-six MI patients underwent electrocardiography and CMR at 1 week (baseline), 4 months, 1 year, and 5 years post-infarction. Conventional CMR parameters were analyzed, and infarct presence, location, and size were assessed using late gadolinium enhancement CMR. Infarct locations were anterior or nonanterior (inferior and/or lateral), using late gadolinium enhancement CMR as a reference. For each time point, patients were classified as having a diagnostic/nondiagnostic electrocardiogram (ECG) using the European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation consensus criteria for previous Q-wave infarct., Results: At baseline, 11 patients (23%) did not meet the criteria for Q-wave MI. Non-Q-wave infarcts were significantly smaller than Q-wave infarcts (p < 0.0001). All anterior Q-wave infarcts (n = 17) were correctly localized, whereas in 7 of 19 nonanterior Q-wave infarcts, the location or extent of the infarct was misjudged by electrocardiography. At 4-month/1-year follow-up, in 10 patients (3 anterior/7 nonanterior), the ECG became nondiagnostic. The ECG remained nondiagnostic at 5-year follow-up. A cutoff infarct size of 6.2% at 1 year yielded a sensitivity of 89% and a specificity of 74% to predict the presence or absence of Q waves., Conclusions: The incidence of nondiagnostic ECGs for previous MI using the current European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation criteria is substantial and increases with time post-infarction from 23% immediately post-infarction to 44% at 5-year follow-up., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The large randomized controlled multicentre clinical trial, HF-ACTION, recently demonstrated that a programme of recommendation of regular exercise training at moderate intensity is safe, improves quality of life, and reduces the combined endpoint of all-cause death and hospitalization in patients with chronic heart failure. However, the size of beneficial effects was modest compared to results published in smaller single studies and meta-analyses., Objective: Based on results of a pilot study, the objective of the present investigation is to test the hypothesis that a programme comprising interval training at high relative intensity would yield significantly larger effects in terms of left ventricular remodelling compared to moderate continuous exercise training., Study Design: In a three-armed randomized multicentre study of stable heart failure patients with left ventricular ejection fraction ≤35%, the effects of a 12-week programme of high-intensity interval training (HIT; 85-90% of peak oxygen uptake, VO(2peak)) will be compared to actual practice in Europe, represented by either an isocaloric programme of moderate continuous training (MCT; 50-60% of VO(2peak)) and a recommendation of regular exercise (RE) of the individual patients' own preference based on clinical practice at the local centre. The primary endpoint is reverse remodelling, defined as change in left ventricular end-diastolic diameter assessed by echocardiography. Secondary endpoints include peak oxygen uptake (VO(2peak)), biomarkers, quality of life, and level of physical activity assessed by questionnaires. In addition, long-term maintenance of effects after the supervised training period will be determined. Assessments will be made at baseline, after the 12-week intervention programme, and at 1-year follow up. A total number of 200 patients on treatment per protocol, randomized to the three groups in a 1 : 1 : 1 manner, is estimated to detect clinically relevant differences in effect with HIT vs. MCT and RE (p < 0.05; statistical power 0.90) for the primary endpoint. Inclusion of patients started May 2009 and will run until total number has been reached.

Objectives: The aim of this study was to determine the long-term effects of cardiac resynchronization therapy (CRT) in the European cohort of patients enrolled in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial., Background: Previous data suggest that CRT slows disease progression and improves the outcomes of asymptomatic or mildly symptomatic patients with left ventricular (LV) dysfunction and a wide QRS complex., Methods: We randomly assigned 262 recipients of CRT pacemakers or defibrillators, with QRS > or =120 ms and LV ejection fraction < or =40% to active (CRT ON; n = 180) versus control (CRT OFF; n = 82) treatment, for 24 months. Mean baseline LV ejection fraction was 28.0%. All patients were in sinus rhythm and receiving optimal medical therapy. The primary study end point was the proportion worsened by the heart failure (HF) clinical composite response. The main secondary study end point was left ventricular end-systolic volume index (LVESVi)., Results: In the CRT ON group, 19% of patients were worsened versus 34% in the CRT OFF group (p = 0.01). The LVESVi decreased by a mean of 27.5 +/- 31.8 ml/m(2) in the CRT ON group versus 2.7 +/- 25.8 ml/m(2) in the CRT OFF group (p < 0.0001). Time to first HF hospital stay or death (hazard ratio: 0.38; p = 0.003) was significantly delayed by CRT., Conclusions: After 24 months of CRT, and compared with those of control subjects, clinical outcomes and LV function were improved and LV dimensions were decreased in this patient population in New York Heart Association functional classes I or II. These observations suggest that CRT prevents the progression of disease in patients with asymptomatic or mildly symptomatic LV dysfunction. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154)., (2009 by the American College of Cardiology Foundation.)