Echocardiography-derived hemodynamic forces (HDF) allow calculation of intraventricular pressure gradients from routine transthoracic echocardiographic images. The evolution of HDF after cardiac... Show moreEchocardiography-derived hemodynamic forces (HDF) allow calculation of intraventricular pressure gradients from routine transthoracic echocardiographic images. The evolution of HDF after cardiac resynchronization therapy (CRT) has not been investigated in large cohorts. The aim was to assess HDF in patients with heart failure implanted with CRT versus healthy controls. HDF were assessed before and 6 months after CRT. The following HDF parameters were calculated: (1) apical-basal strength, (2) lateral-septal strength, (3) the ratio of lateral-septal to apical-basal strength ratio, and (4) the force vector angle (1 and 2 representing the magnitude of HDF, 3 and 4 representing the orientation of HDF). In the propulsive phase of systole, the apical-basal impulse and the systolic force vector angle were measured. A total of 197 patients were included (age 64 ± 11 years, 62% male), with left ventricular ejection fraction ≤35%, QRS duration ≥130 ms and left bundle branch block. The magnitude of HDF was significantly lower and the orientation was significantly worse in patients with heart failure versus healthy controls. Immediately after CRT implantation, the apical-basal impulse and systolic force vector angle were significantly increased. Six months after CRT, improvement of apical-basal strength, lateral-septal to apical-basal strength ratio and the force vector angle occurred. When CRT was deactivated at 6 months, the increase in the magnitude of apical-basal HDF remained unchanged while the systolic force vector angle worsened significantly. In conclusion, HDF in CRT recipients reflect the acute effect of CRT and the effect of left ventricular reverse remodeling on intraventricular pressure gradients. Whether HDF analysis provides incremental value over established echocardiographic parameters, remains to be determined. Show less
Weber, J.E.; Ahmadi, M.; Boldt, L.H.; Eckardt, K.U.; Edelmann, F.; Gerhardt, H.; ... ; Pischon, T. 2023
Introduction The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular ... Show moreIntroduction The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations.Methods and analysis A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm. Deep phenotyping is then performed after similar to 90 days and includes assessments of the patient's medical history, health status and behaviour, cardiovascular, nutritional, metabolic, and anthropometric parameters, and patient-related outcome measures. Biospecimens are collected for analyses including 'OMICs' technologies (e.g., genomics, metabolomics, proteomics). Subcohorts undergo MRI of the brain, heart, lung and kidney, as well as more comprehensive metabolic, neurological and CV examinations. All participants are followed up for up to 10 years to assess clinical outcomes, primarily major adverse CVEs and patient-reported (value-based) outcomes. State-of-the-art clinical research methods, as well as emerging techniques from systems medicine and artificial intelligence, will be used to identify associations between patient characteristics, longitudinal changes and outcomes.Ethics and dissemination The study was approved by the Charite-Universitatsmedizin Berlin ethics committee (EA1/066/17). The results of the study will be disseminated through international peer-reviewed publications and congress presentations.Clinical Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx? TrialID=DRKS00016852. Recruitment started on July 18, 2017.Second study phase: Approved WHO primary register: German Clinical Trials Register DRKS00023323, date of registration: November 4, 2020, URL: http://www.drks.de/DRKS00023323. Recruitment started on January 1, 2021. Show less
Kimura, Y.; Beukers, H.K.C.; Rademaker, R.; Chen, S.P.; Ebert, M.; Jensen, T.; ... ; Zeppenfeld, K. 2023
BACKGROUND Patients with dilated cardiomyopathy (DCM) who are undergoing catheter ablation of ventricular arrhythmias (VAs) are at risk of rapidly progressive heart failure (HF). Endocardial... Show moreBACKGROUND Patients with dilated cardiomyopathy (DCM) who are undergoing catheter ablation of ventricular arrhythmias (VAs) are at risk of rapidly progressive heart failure (HF). Endocardial voltages decrease with loss of viable myocardium. Global left ventricular (LV) voltage as a surrogate for the amount of remaining viable myocardium may predict prognosis.OBJECTIVES This study evaluated whether the newly proposed parameter volume-weighted (vw) unipolar voltage (UV) can predict HF-related adverse outcomes (HFOs), including death, heart transplantation, or ventricular assist device implantation, in DCM. METHODS In consecutive patients with DCM referred for VA ablation, vwUV was calculated by mathematically integrating UV over the left ventricle, divided by the endocardial LV surface area and wall thickness. Patients were followed for HFOs.RESULTS A total of 103 patients (57 +/- 14 years of age; left ventricular ejection fraction [LVEF], 39% +/- 13%) were included. Median vwUV was 9.75 (IQR: 7.27-12.29). During a median follow-up of 24 months (IQR: 8-47 months), 25 patients (24%) died, and 16 had HFOs 7 months (IQR: 1-18 months) after ablation. Patients with HFOs had significantly lower LVEF (29% +/- 10% vs 41% +/- 12%), vw bipolar voltage (BV) (3.00 [IQR: 2.47-3.53] vs 5.00 [IQR: 4.12-5.73]), and vwUV (5.94 [IQR: 5.28-6.55] vs 10.37 [IQR: 8.82-12.81]; all P < 0.001), than patients without HFOs. In Cox regression analysis and goodness-of-fit tests, vwUV was the strongest and independent predictor for HFOs (HR: 3.68; CI: 2.09-6.45; likelihood ratio chi-square, 33.05; P < 0.001).CONCLUSIONS The novel parameter vwUV, as a surrogate for the amount of viable myocardium, identifies patients with DCM with VA who are at high risk for HF progression and mortality. Show less
Neijenhuis, R.M.L.; Nederend, M.; Jongbloed, M.R.M.; Kies, P.; Rotmans, J.I.; Vliegen, H.W.; ... ; Egorova, A.D. 2023
AimsGiven the compelling evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the conventional heart failure population, SGLT2i deserve exploration in systemic... Show moreAimsGiven the compelling evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the conventional heart failure population, SGLT2i deserve exploration in systemic right ventricular (sRV) failure. The initial experience with dapagliflozin in sRV failure patients is described, with a focus on tolerability and short-term effects on clinical outcomes.Methods and resultsTen patients (70% female, median age 50 years [46.5-52]) with symptomatic sRV failure who received dapagliflozin 10 mg per day on top of optimal medical therapy between 04-2021 and 01-2023 were included. Within 4 weeks, no significant changes in blood pressure, electrolytes, or serum glucose occurred. Creatinine and estimated glomerular filtration rate (eGFR) showed a slight decline (88 & PLUSMN; 17 to 97 & PLUSMN; 23 & mu;mol/L, p = 0.036, and 72 & PLUSMN; 14 vs. 66 & PLUSMN; 16 ml/min/1.73m(2), p = 0.020, respectively). At 6 months follow-up (n = 8), median NT-proBNP decreased significantly from 736.6 [589.3-1193.3] to 531.6 [400.8-1018] ng/L (p = 0.012). Creatinine and eGFR recovered to baseline levels. There were no significant changes in echocardiographic systolic sRV or left ventricular function. New York Heart Association class improved significantly in 4 out of 8 patients (p = 0.046), who also showed an improvement in the 6-minute walk test or bicycle exercise test performance. One female patient developed an uncomplicated urinary tract infection. No patients discontinued treatment.ConclusionDapagliflozin was well-tolerated in this small cohort of sRV failure patients. While the early results on the reduction of NT-proBNP and clinical outcome parameters are encouraging, large-scale prospective studies are warranted to thoroughly evaluate the effects of SGLT2i in the growing sRV failure population. Show less
Saeed, D.; Feldman, D.; Banayosy, A. el; Birks, E.; Blume, E.; Cowger, J.; ... ; D'Alessandro, D. 2023
Background: Self-care (SC) is a cornerstone in heart failure management and is related to patient outcomes. The continuous and complex demands of SC can be experienced as stressful and may require... Show moreBackground: Self-care (SC) is a cornerstone in heart failure management and is related to patient outcomes. The continuous and complex demands of SC can be experienced as stressful and may require patients to apply resilient behaviors as they manage their conditions. Resilience may be a helpful factor in performing SC.Objective: The aim of this study was to determine the association between resilience and SC in patients with heart failure.Methods: A cross-sectional study was performed between January 2020 and January 2021. Participants were asked to complete a questionnaire addressing baseline characteristics, the 2-item Patient Health Questionnaire, the Resilience Evaluation Scale, and the Self-Care of Chronic Illness Inventory, which measures 3 concepts of SC: SC maintenance, SC monitoring, and SC management. Multiple regression analysis was performed to determine whether resilience was associated with SC.Results: Eighty-six patients were included, and 74 patients completed the questionnaire. In the univariate analysis, an association was found between resilience and SC maintenance, resulting in an increase in SC for patients with higher resilience (β = 0.24; 95% confidence interval, 0.03-0.96). In the multivariate analysis adjusted and corrected for confounders, no significant associations between resilience and all SC scales were found.Conclusion: This study could not demonstrate significant associations between resilience and all SC scales. This study contributes to the body of knowledge on factors that can mediate or moderate SC. Further longitudinal research should be performed to study cause-effect relationships. Show less
BackgroundOsteosarcoma and Ewing sarcoma patients face a significant risk of cardiotoxicity as defined by left ventricular dysfunction and heart failure (HF).ObjectivesThis study sought to evaluate... Show moreBackgroundOsteosarcoma and Ewing sarcoma patients face a significant risk of cardiotoxicity as defined by left ventricular dysfunction and heart failure (HF).ObjectivesThis study sought to evaluate the association between age at sarcoma diagnosis and incident HF.MethodsA retrospective cohort study was performed at the largest sarcoma center in the Netherlands among patients with an osteosarcoma or Ewing sarcoma. All patients were diagnosed and treated over a 36-year period (1982-2018) and followed until August 2021. Incident HF was adjudicated through the universal definition of heart failure. Determinants including age at diagnosis, doxorubicin dose, and cardiovascular risk factors were entered as fixed or time-dependent covariates into a cause-specific Cox model to assess their impact on incident HF.ResultsThe study population consisted of 528 patients with a median age at diagnosis of 19 years (Q1-Q3: 15-30 years). Over a median follow-up time of 13.2 years (Q1-Q3: 12.5-14.9 years), 18 patients developed HF with an estimated cumulative incidence of 5.9% (95% CI: 2.8%-9.1%). In a multivariable model, age at diagnosis (HR: 1.23; 95% CI: 1.06-1.43) per 5-year increase, doxorubicin dose per 10-mg/m2 increase (HR: 1.13; 95% CI: 1.03-1.24), and female sex (HR: 3.17; 95% CI: 1.11-9.10) were associated with HF.ConclusionsIn a large cohort of sarcoma patients, we found that patients diagnosed at an older age are more prone to develop HF. Show less
Bhatt, A.S.; Vaduganathan, M.; Zhuo, M.; Fu, E.L.; Solomon, S.D.; Desai, R.J. 2023
Background: The acute hemodynamic effects of sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), may result in early changes in kidney function, raising concerns about acute... Show moreBackground: The acute hemodynamic effects of sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), may result in early changes in kidney function, raising concerns about acute kidney injury (AKI), particularly in those who are naive to renin-angiotensin sysMethods: We conducted a cohort study using U.S. Medicare fee-for-service claims data (2014-2017). Patients with HFrEF > 65 years newly initiating ARNI or RASi, with no prior use of either drug class, were included. The primary outcome was hospitalization due to AKI as the primary discharge diagnosis, and the secondary outcome included AKI as a primary or secondary discharge diagnosis. AKI risks were described under an as-treated follow-up approach, with censoring on treatment discontinuation, switch, insurance disenrollment, death, or administrative censoring as well as an intent-to-treat approach. Propensity-score-based finestratification weighting was used to account for potential confounding by 81 pre-exposure characteristics. Cumulative incidence functions were used to report absolute risks, and Cox proportional hazards models were used to provide hazard ratios (HR) and 95% confidence intervals (CI). Results: We included 27,166 patients with a mean (SD) age of 73 (7.3) years, and 4155 (15.3%) were initiating ARNI. After propensity score weighting, the 180-day cumulative incidence was 2.7% (2.4%-3.1%) among RASi initiators and 2.7% (2.2%-3.5%) among ARNI initiators for the primary outcome, and it was 6.5% (6.0%-7.1%) and 6.1% (5.2%-7.1%), respectively, for the secondary outcome under as-treated follow-up. HR (95% CI) comparing ARNI with RASi were 0.91 (95% CI: 0.72-1.16) for the primary outcome and 0.92 (95% CI: 0.79-1.08) for the secondary outcome. Similar results were observed in the intent-to-treat analysis. Conclusions: Among a large cohort of U.S. Medicare beneficiaries with HFrEF, ARNI treatment was not associated with higher rates of AKI than RASi treatment. These results provide reassurance for providers considering ARNI initiation in older patients who are RASi-naive. (J Cardiac Fail 2023;29:138-146) Show less
BackgroundSecondary mitral regurgitation (SMR) is a progressive disease with characteristic pathophysiological changes that may influence prognosis. Although the staging of SMR patients suffering... Show moreBackgroundSecondary mitral regurgitation (SMR) is a progressive disease with characteristic pathophysiological changes that may influence prognosis. Although the staging of SMR patients suffering from heart failure with reduced ejection fraction (HFrEF) according to extramitral cardiac involvement has prognostic value in medically treated patients, such data are so far lacking for edge-to-edge mitral valve repair (M-TEER).ObjectivesThis study sought to classify M-TEER patients into disease stages based on the phenotype of extramitral cardiac involvement and to assess its impact on symptomatic and survival outcomes.MethodsBased on echocardiographic and clinical assessment, patients were assigned to 1 of the following HFrEF-SMR groups: left ventricular involvement (Stage 1), left atrial involvement (Stage 2), right ventricular volume/pressure overload (Stage 3), or biventricular failure (Stage 4). A Cox regression model was implemented to investigate the impact of HFrEF-SMR stages on 2-year all-cause mortality. The symptomatic outcome was assessed with New York Heart Association functional class at follow-up.ResultsAmong a total of 849 eligible patients who underwent M-TEER for relevant SMR from 2008 until 2019, 9.5% (n = 81) presented with left ventricular involvement, 46% (n = 393) with left atrial involvement, 15% (n = 129) with right ventricular pressure/volume overload, and 29% (n = 246) with biventricular failure. An increase in HFrEF-SMR stage was associated with increased 2-year all-cause mortality after M-TEER (HR: 1.39; CI: 1.23-1.58; P < 0.01). Furthermore, higher HFrEF-SMR stages were associated with significantly less symptomatic improvement at follow-up.ConclusionsThe classification of M-TEER patients into HFrEF-SMR stages according to extramitral cardiac involvement provides prognostic value in terms of postinterventional survival and symptomatic improvement. Show less
Background: Atrial functional tricuspid regurgitation (atrial TR) has received growing recognition as a TR entity with a distinct cause owing to its independence from valvular tethering as the... Show moreBackground: Atrial functional tricuspid regurgitation (atrial TR) has received growing recognition as a TR entity with a distinct cause owing to its independence from valvular tethering as the predominant mechanism underlying TR. However, characterization of atrial TR varies, and a universal definition is lacking. Methods: In total, 651 patients with significant functional TR were analyzed, including 438 conservatively treated individuals and 213 patients who received transcatheter tricuspid valve repair (TTVR). Based on a clustering approach, we defined atrial TR as tricuspid valve (TV) tenting height <= 10 mm, midventricular right ventricular diameter <= 38 mm, and left ventricular ejection fraction >= 50%. Results: Patients with atrial TR were more often females, had higher right ventricular fractional area change, higher left ventricular ejection fraction, and lower LV end-diastolic diameter, TV tenting area and height, lower right ventricular and tricuspid annular size, enlarged, but lower right atrial area and lower TV effective regurgitant orifice area (all P<0.05). Patients with atrial TR had significantly better long-term survival than non-atrial TR in the conservatively treated TR cohort (P<0.01, n=438). Atrial TR was independently associated with a lower rate of the combined end point of mortality and heart failure hospitalization at 1-year follow-up in the TTVR cohort (hazard ratio, 0.39; P<0.05, n=213). TR degree was significantly reduced after TTVR in non-atrial and atrial TR (P<0.01). Functional parameters significantly improved following TTVR independent of TR cause (P<0.05). Conclusions: An echocardiography-based atrial TR definition is associated with prognostic relevance in patients with functional TR in conservatively treated TR and after TTVR. Show less
BACKGROUND The clinical course of patients with moderate aortic stenosis (AS) remains incompletely defined.OBJECTIVES This study sought to analyze the clinical course of moderate AS and compare it... Show moreBACKGROUND The clinical course of patients with moderate aortic stenosis (AS) remains incompletely defined.OBJECTIVES This study sought to analyze the clinical course of moderate AS and compare it with other stages of the disease.METHODS Multiple electronic databases were searched to identify studies on adult moderate AS. Random-effects models were used to derive pooled estimates. The primary endpoint was all-cause death. The secondary endpoints were cardiac death, heart failure, sudden death, and aortic valve replacement.RESULTS Among a total of 25 studies (12,143 moderate AS patients, 3.7 years of follow-up), pooled rates per 100 person-years were 9.0 (95% CI: 6.9 to 11.7) for all-cause death, 4.9 (95% CI: 3.1 to 7.5) for cardiac death, 3.9 (95% CI: 1.9 to 8.2) for heart failure, 1.1 (95% CI: 0.8 to 1.5) for sudden death, and 7.2 (95% CI: 4.3 to 12.2) for aortic valve replacement. Meta-regression analyses detected that diabetes (P = 0.019), coronary artery disease (P = 0.017), presence of symptoms (P < 0.001), and left ventricle (LV) dysfunction (P = 0.009) were associated with a significant impact on the overall estimate of all-cause death. All-cause mortality was higher in patients with reduced LV ejection fraction (<50%) than with normal LV ejection fraction: 16.5 (95% CI: 5.2 to 52.3) and 4.2 (95% CI: 1.4 to 12.8) per 100 person-years, respectively. Compared with moderate AS, the incidence rate difference of all-cause mortality was-3.9 (95% CI:-6.7 to-1.1) for no or mild AS and +2.2 (95% CI: +0.8 to +3.5) for severe AS patients.CONCLUSIONS Moderate AS appears to be associated with a mortality risk higher than no or mild AS but lower than severe AS, which increases in specific population subsets. The impact of early intervention in moderate AS patients having high-risk features deserves further investigation. (C) 2022 by the American College of Cardiology Foundation. Show less
Stassen, J.; Galloo, X.; Hirasawa, K.; Bijl, P. van der; Leon, M.B.; Marsan, N.A.; Bax, J.J. 2022
Aims: Left atrial (LA) function is a strong prognostic marker in patients with heart failure and functional mitral regurgitation (MR). Although cardiac resynchronization therapy (CRT) has shown to... Show moreAims: Left atrial (LA) function is a strong prognostic marker in patients with heart failure and functional mitral regurgitation (MR). Although cardiac resynchronization therapy (CRT) has shown to improve MR severity, the interaction between a reduction in MR severity and an increase in LA function, as well as its association with outcomes, has not been investigated. Methods and results: LA reservoir strain (RS) was evaluated with speckle tracking echocardiography in patients with at least moderate functional MR undergoing CRT implantation. MR improvement was defined as at least 1 grade improvement in MR severity at 6 months after CRT implantation. The primary endpoint was all-cause mortality. A total of 340 patients (mean age 66 +/- 10 years, 73% male) were included, of whom 200 (59%) showed MR improvement at 6 months follow-up. On multivariable analysis, an improvement in MR severity was independently associated with an increase in LARS (odds ratio 1.008; 95% confidence interval 1.003-1.013; P = 0.002). After multivariable adjustment, including baseline and follow-up variables, an increase in LARS was significantly associated with lower mortality. MR improvers showing LARS increasement had the lowest mortality rate, whereas outcomes were not significantly different between MR non-improvers and MR improvers showing no LARS increasement (P = 0.236). Conclusion: A significant reduction in MR severity at 6 months after CRT implantation is independently associated with an increase in LARS. In addition, an increase in LARS is independently associated with lower all-cause mortality in patients with heart failure and significant functional MR. Show less
Nederend, M.; Jongbloed, M.R.M.; Kies, P.; Vliegen, H.W.; Bouma, B.J.; Regeer, M.V.; ... ; Egorova, A.D. 2022
Background: Patients with transposition of the great arteries (TGA) after an atrial switch or congenitally corrected TGA (ccTGA) are prone to systemic right ventricular (sRV) failure. Tricuspid... Show moreBackground: Patients with transposition of the great arteries (TGA) after an atrial switch or congenitally corrected TGA (ccTGA) are prone to systemic right ventricular (sRV) failure. Tricuspid valve (TV) regurgitation aggravates sRV dysfunction. Timely TV surgery stabilizes sRV function, yet the development of atrioventricular (AV)-conduction disturbances in the course of sRV failure can contribute to sRV dysfunction through pacing-induced dyssynchrony. This study aims to explore the incidence, timing, and functional consequences of AV-block requiring ventricular pacing after TV surgery in patients with sRV. Methods: Consecutive adolescent and adult patients with an sRV who underwent TV surgery between 1989 and 2020 and followed-up at our center were included in this observational cohort study. Results: The data of 28 patients (53% female, 57% ccTGA, and a mean age at surgery 38 +/- 13 years) were analyzed. The mean follow-up was 9.7 +/- 6.8 years. Of the remaining 22 patients at the risk of developing high degree AV-block after TV surgery, 9 (41%) developed an indication for chronic ventricular pacing during follow-up, of which 5 (56%) within 24 months postoperatively (3 prior to hospital discharge). The QRS duration, a surrogate marker for dyssynchrony, was significantly higher in patients with chronic left ventricular pacing than in patients with native AV-conduction (217 +/- 24 vs. 116 +/- 23 ms, p = 0.000), as was the heart failure biomarker NT-pro-BNP [2,746 (1,242-6,879) vs. 495 (355-690) ng/L, p = 0.004] and the percentage of patients with >= 1 echocardiographic class of deterioration of systolic sRV function (27 vs. 83%, p = 0.001). Of the patients receiving chronic subpulmonary ventricular pacing (n = 12), 9 (75%) reached the composite endpoint of progressive heart failure [death, ventricular assist device implantation, or upgrade to cardiac resynchronization therapy (CRT)]. Only 4 (31%) patients with native AV-conduction (n = 13) reached this composite endpoint (p = 0.027). Conclusion: Patients with a failing sRV who undergo TV surgery are prone to develop AV-conduction abnormalities, with 41% developing an indication for chronic ventricular pacing during 10 years of follow-up. Patients with chronic subpulmonary ventricular pacing have a significantly longer QRS complex duration, have higher levels of the heart failure biomarker NT-pro-BNP, and are at a higher risk of deterioration of systolic sRV function and progressive heart failure. Show less
Wezenbeek, J. van; Kianzad, A.; Bovenkamp, A. van de; Wessels, J.; Mouratoglou, S.A.; Braams, N.J.; ... ; Man, F.S. de 2022
Background: Heart failure with preserved ejection fraction (HFpEF) is a prevalent disorder for which no effective treatment yet exists. Pulmonary hypertension (PH) and right atrial (RA) and... Show moreBackground: Heart failure with preserved ejection fraction (HFpEF) is a prevalent disorder for which no effective treatment yet exists. Pulmonary hypertension (PH) and right atrial (RA) and ventricular (RV) dysfunction are frequently observed. The question remains whether the PH with the associated RV/RA dysfunction in HFpEF are markers of disease severity. Methods: To obtain insight in the relative importance of pressure-overload and left-to-right interaction, we compared RA and RV function in 3 groups: 1. HFpEF (n=13); 2. HFpEF-PH (n=33), and; 3. pulmonary arterial hypertension (PAH) matched to pulmonary artery pressures of HFpEF-PH (PH limited to mPAP >= 30 and <= 50 mmHg) (n=47). Patients underwent right heart catheterization and cardiac magnetic resonance imaging. Results: The right ventricle in HFpEF-PH was less dilated and hypertrophied than in PAH. In addition, RV ejection fraction was more preserved (HFpEF-PH: 52 +/- 11 versus PAH: 36 +/- 12%). RV filling patterns differed: vena cava backflow during RA contraction was observed in PAH only. In HFpEF-PH, RA pressure was elevated throughout the cardiac cycle (HFpEF-PH: 10 [8-14] versus PAH: 7 [5-10] mm Hg), while RA volume was smaller, reflecting excessive RA stiffness (HFpEF-PH: 0.14 [0.10-0.17] versus PAH: 0.08 [0.06-0.11] mm Hg/mL). RA stiffness was associated with an increased eccentricity index (HFpEF-PH: 1.3 +/- 0.2 versus PAH: 1.2 +/- 0.1) and interatrial pressure gradient (9 [5 to 12] versus 2 [-2 to 5] mm Hg). Conclusions: RV/RA function was less compromised in HFpEF-PH than in PAH, despite similar pressure-overload. Increased RA pressure and stiffness in HFpEF-PH were explained by left atrial/RA-interaction. Therefore, our results indicate that increased RA pressure is not a sign of overt RV failure but rather a reflection of HFpEF-severity. Show less
Heart failure (HF) is among the most important and frequent complications of diabetes mellitus (DM). The detection of subclinical dysfunction is a marker of HF risk and presents a potential target... Show moreHeart failure (HF) is among the most important and frequent complications of diabetes mellitus (DM). The detection of subclinical dysfunction is a marker of HF risk and presents a potential target for reducing incident HF in DM. Left ventricular (LV) dysfunction secondary to DM is heterogeneous, with phenotypes including predominantly systolic, predominantly diastolic, and mixed dysfunction. Indeed, the pathogenesis of HF in this setting is heterogeneous. Effective management of this problem will require detailed phenotyping of the contributions of fibrosis, microcirculatory disturbance, abnormal metabolism, and sympathetic innervation, among other mechanisms. For this reason, an imaging strategy for the detection of HF risk needs to not only detect subclinical LV dysfunction (LVD) but also characterize its pathogenesis. At present, it is possible to identify individuals with DM at increased risk HF, and there is evidence that cardioprotection may be of benefit. However, there is insufficient justification for HF screening, because we need stronger evidence of the links between the detection of LVD, treatment, and improved outcome. This review discusses the options for screening for LVD, the potential means of identifying the underlying mechanisms, and the pathways to treatment. Show less
Nearly half of all patients with heart failure (HF) have a normal left ventricular (LV) ejection fraction (EF) and the condition is termed heart failure with preserved ejection fraction (HFpEF). It... Show moreNearly half of all patients with heart failure (HF) have a normal left ventricular (LV) ejection fraction (EF) and the condition is termed heart failure with preserved ejection fraction (HFpEF). It is assumed that in these patients HF is due primarily to LV diastolic dysfunction. The prognosis in HFpEF is almost as severe as in HF with reduced EF (HFrEF). In contrast to HFrEF where drugs and devices are proven to reduce mortality, in HFpEF there has been limited therapy available with documented effects on prognosis. This may reflect that HFpEF encompasses a wide range of different pathological processes, which multimodality imaging is well placed to differentiate. Progress in developing therapies for HFpEF has been hampered by a lack of uniform diagnostic criteria. The present expert consensus document from the European Association of Cardiovascular Imaging (EACVI) provides recommendations regarding how to determine elevated LV filling pressure in the setting of suspected HFpEF and how to use multimodality imaging to determine specific aetiologies in patients with HFpEF. Show less
Background: Elevated cardiac troponin levels in blood are associated with increased risk of cardiovascular diseases and mortality. Cardiac troponin levels are heritable, but their genetic... Show moreBackground: Elevated cardiac troponin levels in blood are associated with increased risk of cardiovascular diseases and mortality. Cardiac troponin levels are heritable, but their genetic architecture remains elusive. Methods: We conducted a transethnic genome-wide association analysis on high-sensitivity cTnT (cardiac troponin T; hs-cTnT) and high-sensitivity cTnI (cardiac troponin I; hs-cTnI) levels in 24 617 and 14 336 participants free of coronary heart disease and heart failure from 6 population-based cohorts, followed by a series of bioinformatic analyses to decipher the genetic architecture of hs-cTnT and hs-cTnI. Results: We identified 4 genome-wide significant loci for hs-cTnT including a novel locus rs3737882 in PPFIA4 and 3 previously reported loci at NCOA2, TRAM1, and BCL2. One known locus at VCL was replicated for hs-cTnI. One copy of C allele for rs3737882 was associated with a 6% increase in hs-cTnT levels (minor allele frequency, 0.18; P=2.80x10(-9)). We observed pleiotropic loci located at BAG3 and ANO5. The proportions of variances explained by single-nucleotide polymorphisms were 10.15% and 7.74% for hs-cTnT and hs-cTnI, respectively. Single-nucleotide polymorphisms were colocalized with BCL2 expression in heart tissues and hs-cTnT and with ANO5 expression in artery, heart tissues, and whole blood and both troponins. Mendelian randomization analyses showed that genetically increased hs-cTnT and hs-cTnI levels were associated with higher odds of atrial fibrillation (odds ratio, 1.38 [95% CI, 1.25-1.54] for hs-cTnT and 1.21 [95% CI, 1.06-1.37] for hs-cTnI). Conclusions: We identified a novel genetic locus associated with hs-cTnT in a multiethnic population and found that genetically regulated troponin levels were associated with atrial fibrillation. Show less
Zandstra, T.E.; Nederend, M.; Jongbloed, M.R.M.; Kies, P.; Vliegen, H.W.; Bouma, B.J.; ... ; Egorova, A.D. 2021
Objective Pharmacological options for patients with a failing systemic right ventricle (RV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected... Show moreObjective Pharmacological options for patients with a failing systemic right ventricle (RV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are not well defined. This study aims to investigate the feasibility and effects of sacubitril/valsartan treatment in a single-centre cohort of patients. Methods Data on all consecutive adult patients (n=20, mean age 46 years, 50% women) with a failing systemic RV in a biventricular circulation treated with sacubitril/valsartan in our centre are reported. Patients with a systemic RV ejection fraction of <= 35% who were symptomatic despite treatment with beta-blocker and ACE-inhibitor/angiotensin II receptor-blockers were started on sacubitril/valsartan. This cohort underwent structural follow-up including echocardiography, exercise testing, laboratory investigations and quality of life (QOL) assessment. Results Six-month follow-up data were available in 18 out of 20 patients, including 12 (67%) patients with TGA after atrial switch and 6 (33%) patients with ccTGA. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) decreased significantly (950-358 ng/L, p<0.001). Echocardiographic systemic RV fractional area change and global longitudinal strain showed small improvements (19%-22%, p<0.001 and -11% to -13%, p=0.014, respectively). The 6 min walking distance improved significantly from an average of 564 to 600 m (p=0.011). The QOL domains of cognitive function, sleep and vitality improved (p=0.015, p=0.007 and p=0.037, respectively). Conclusions We describe the first patient cohort with systemic RV failure treated with sacubitril/valsartan. Treatment appears feasible with improvements in NT-pro-BNP and echocardiographic function. Our positive results show the potential of sacubitril/valsartan for this patient population. Show less
OBJECTIVES The aim of this study was to determine the prognostic impact of right ventricular (RV)-pulmonary arterial (PA) coupling in patients with heart failure (HF) with severe secondary mitral... Show moreOBJECTIVES The aim of this study was to determine the prognostic impact of right ventricular (RV)-pulmonary arterial (PA) coupling in patients with heart failure (HF) with severe secondary mitral regurgitation (SMR) enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial.BACKGROUND RV contractile function and PA pressures influence outcomes in patients with SMR, but the impact of RV-PA coupling in patients randomized to transcatheter edge-to-edge repair (TEER) vs guideline-directed medical therapy (GDMT) is unknown.METHODS RV-PA coupling was assessed by the ratio of RV free wall longitudinal strain derived from speckle-tracking echocardiography and noninvasively measured RV systolic pressure. Advanced RV-PA uncoupling was defined as RV free wall longitudinal strain/RV systolic pressure <= 0.5%/mm Hg. The primary endpoint was a composite of all-cause mortality or HF hospitalization at 24-month follow-up.RESULTS A total of 372 patients underwent speckle-tracking echocardiography, and 70.2% had advanced RV-PA uncoupling. By multivariable analysis, advanced RV-PA uncoupling was strongly associated with an increased risk for the primary 24-month endpoint of death or HF hospitalization (HR: 1.87; 95% CI: 1.31-2.66; P = 0.0005). A similar association was present for all-cause mortality alone (HR: 2.57; 95% CI: 1.54-4.29; P = 0.0003). The impact of RV-PA uncoupling was consistent in patients randomized to TEER and GDMT alone. Compared with GDMT alone, the addition of TEER improved 2-year outcomes in patients with (48.0% vs 74.8%; HR: 0.51; 95% CI: 0.37-0.71) and those without (28.8% vs 47.8%; HR: 0.51; 95% CI: 0.27-0.97) advanced RV-PA uncoupling (P-interaction = 0.98).CONCLUSIONS In the COAPT trial, advanced RV dysfunction assessed by RV-PA uncoupling was a powerful predictor of 2-year adverse outcomes in patients with HF and SMR. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial]; NCT01626079) (C) 2021 by the American College of Cardiology Foundation. Show less
Sitges, M.; Marsan, N.A.; Cameli, M.; D'Andrea, A.; Carvalho, R.F.; Holte, E.; ... ; Dweck, M.R. 2021
Aims The aim of this study is to analyse how current recommendations on left ventricular (LV) diastolic function assessment have been adopted. Identifying potential discrepancies between... Show moreAims The aim of this study is to analyse how current recommendations on left ventricular (LV) diastolic function assessment have been adopted. Identifying potential discrepancies between recommendations and everyday clinical practice would enable us to better understand and address the remaining challenges in this controversial and complex field.Methods and results A total of 93 centres, mainly from tertiary care settings, responded to the survey. More than three-quarters (77%) of centres follow the 2016 ASE/EACVI recommendations for LV diastolic function evaluation in patients with preserved ejection fraction based upon e, E/e', tricuspid regurgitation velocity, and left atrial (LA) volume. These recommendations were generally preferred to the previous 2009 version. Many centres also consider strain assessments in the LV (48%) and left atrium (53%) as well as diastolic stress echocardiography (33%) to be useful as additional assessments of LV diastolic function. Echocardiographic assessments of LV diastolic function were used frequently to guide therapy in 72% of centres.Conclusion There is widespread adoption of current recommendation on the evaluation of LV diastolic function and these are frequently used to guide patient management. Many centres now also consider LV and LA strain assessments useful in the clinical assessment of diastolic function. These may be considered in future recommendations. Show less
