Search

Background: β3-AR (β3-adrenergic receptor) stimulation improved systolic function in a sheep model of systolic heart failure (heart failure with reduced ejection fraction [HFrEF]). Exploratory findings in patients with New York Heart Association functional class II HFrEF treated with the β3-AR-agonist mirabegron supported this observation. Here, we measured the hemodynamic response to mirabegron in patients with severe HFrEF. Methods: In this randomized, double-blind, placebo-controlled trial we assigned patients with New York Heart Association functional class III–IV HFrEF, left ventricular ejection fraction Results: We randomized 22 patients (age 66±11 years, 18 men, 16, New York Heart Association functional class III), left ventricular ejection fraction 20±7%, median NT-proBNP 1953 ng/L. No significant changes were seen after 3 hours, but after 1 week, there was a significantly larger increase in cardiac index in the mirabegron group compared with the placebo group (mean difference, 0.41 [CI, 0.07–0.75] L/min/BSA; P =0.039). Pulmonary vascular resistance decreased significantly more in the mirabegron group compared with the placebo group (−1.6 [CI, −0.4 to −2.8] Wood units; P =0.02). No significant differences were seen during exercise. There were no differences in changes in heart rate, systemic vascular resistance, blood pressure, or renal function between groups. Mirabegron was well-tolerated. Conclusions: Oral treatment with the β3-AR-agonist mirabegron for 1 week increased cardiac index and decreased pulmonary vascular resistance in patients with moderate to severe HFrEF. Mirabegron may be useful in patients with worsening or terminal HF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: 2016-002367-34.

Background: Left ventricular noncompaction (LVNC) is characterized by excessive trabeculations of the LV and may be associated with reduced systolic function or severe adverse outcomes. Several aspects remain to be elucidated; there is controversy to whether LVNC cardiomyopathy is a distinct cardiomyopathy caused by failure of the spongy fetal myocardium to condense during fetal development or acquired later in life as a morphological trait associated with other types of cardiomyopathy; the prevalence in unselected populations is unknown and the distinction between normal variation and pathology remains to be defined. In this study, we aimed to determine the prevalence of LVNC and the association to LV systolic function in a large, population-based cohort of neonates. In addition, we assessed the normal ratio of noncompact to compact (NC:C) myocardium in 150 healthy neonates. Methods: Echocardiographic data were prospectively collected in the population study Copenhagen Baby Heart Study. The ratio of NC:C was measured in 12 ventricular segments. LVNC was defined as NC:C ≥2 in at least one segment. Neonates with LVNC were matched 1:10 to controls on sex, gestational age, and weight and age at the examination day. Results: In total, 25 590 neonates (52% males, median age 11 [interquartile range, 7–15] days) underwent echocardiography. Among 21 133 with satisfactory visualization of ventricular segments, we identified a prevalence of LVNC of 0.076% (95% CI, 0.047–0.123). LV ejection fraction was lower in neonates with LVNC compared with matched controls (median 49.5 versus 59.0%; P Conclusions: The prevalence of LVNC based on neonatal echocardiography was 0.076%. LVNC was associated with lower LV systolic function. The findings in normal newborns support the cutoff NC:C ≥2 as an appropriate diagnostic criterion. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02753348.

Background: Left atrial diameter (LAd) is included in the European Society for Cardiology's (ESC) risk model for assessment of sudden cardiac death (SCD) risk in hypertrophic cardiomyopathy (HCM), but the recommended measure of LA size is left atrial volume (LAv). Hypothesis: We hypothesized that LAv could be used instead of LAd in the HCM risk-SCD model. We aimed to determine the relation between LAd and LAv and to assess the impact of using LAv instead of LAd. Methods: Echocardiographic measurements of anteroposterior LAd in the parasternal long-axis window and LAv from Simpson's biplane method of disks were used. The 5-year risk of SCD by measured LAd and by LAd predicted from LAv were estimated using the ESC risk-SCD model. Results: In 205 HCM patients (age 56 ± 14 years, 62% male), the relation between LAd and LAv was linear. Median 5-year risk of SCD was 2.4% (interquartile range [IQR]: 1.6; 3.8) using measured LAd and 2.4% (IQR: 1.6; 3.7) using predicted LAd. The correlation between the SCD risk assessed by measured vs predicted LAd was excellent (r2 = 0.96). Use of predicted LAd resulted in four patients (2%) being recategorized between the moderate and high-risk categories. Conclusions: The relation between LAd and LAv was linear with good agreement. On a population level, the correlation between the risk of SCD using measured LAd or LAd predicted from LAv was excellent. On a patient level, using LAd predicted from LAv resulted in the vast majority remaining in the same risk category; however, for a minority of patients, it changed the recommendation.

Introduction: Left ventricular non-compaction (LVNC) is characterized by excessive trabeculations of the left ventricular wall and may be associated with reduced systolic function. It is debated whether LVNC is congenital or may develop later as part of other cardiomyopathies. The clinical importance and heredity of LVNC with normal systolic function is unclear. We aimed to describe the cardiac development in children with LVNC from birth to 2-4 years of age, compared to matched controls. Additionally, we aimed to describe the prevalence of LVNC in first-degree relatives. Methods: A follow-up transthoracic echocardiography was performed in children at 2-4 years of age diagnosed with LVNC at birth ( Results: Of the 16 children diagnosed with LVNC at birth, 10 have been reevaluated (age 3.5 (interquartile range (IQR) 3, 4) years, 80% male) together with 20 matched controls (age 4 (IQR 3, 4) years, 70% male), 29 first-degree relatives in case group (age 29 (IQR 4, 35) years, 45% male) and 55 first-degree relatives in control group (age 32 (IQR 11, 36) years, 51% male). In probands, the extent of trabeculation (13% vs. 12%, p=0.97) and fractional shortening (FS) (29% vs. 31%, p=0.24) were unchanged from birth to follow-up. At follow-up, the median left ventricular FS was significantly lower in probands compared to matched controls (31% vs. 33%, p=0.03). Ten (35%) first-degree relatives to probands fulfilled criteria for LVNC compared to 0 (0%) of first-degree relatives to controls (p Conclusions: Children with LVNC diagnosed neonatally as part of a population study had no further progression of left ventricular dysfunction or extent of trabeculation at the age of 2-4 years, but systolic function was reduced compared to matched controls. One third of first-degree relatives to children with LVNC fulfilled criteria for LVNC.

Background: The VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) targeted young sarcomeric gene mutation carriers with early-stage hypertrophic cardiomyopathy (HCM) to test whether valsartan can modify disease progression. We describe the baseline characteristics of the VANISH cohort and compare to previous trials evaluating angiotensin receptor blockers. Methods: Applying a randomized, double-blinded, placebo-controlled design, 178 participants with nonobstructive HCM (age, 23.3±10.1 years; 61% men) were randomized in the primary cohort and 34 (age, 16.5±4.9 years; 50% men) in the exploratory cohort of sarcomeric mutation carriers without left ventricular hypertrophy. Results: In the primary cohort, maximal left ventricular wall thickness was 17±4 mm for adults and Z score 7.0±4.5 for children. Nineteen percent had late gadolinium enhancement on cardiac magnetic resonance. Mean peak oxygen consumption was 33 mL/kg per minute, and 92% of participants were New York Heart Association functional class I. New York Heart Association class II was associated with older age, MYH7 variants, and more prominent imaging abnormalities. Six previous trials of angiotensin receptor blockers in HCM enrolled a median of 24 patients (range, 19–133) with mean age of 51.2 years; 42% of patients were in New York Heart Association class ≥II, and sarcomeric mutations were not required. Conclusions: The VANISH cohort is much larger, younger, less heterogeneous, and has less advanced disease than prior angiotensin receptor blocker trials in HCM. Participants had relatively normal functional capacity and mild HCM features. New York Heart Association functional class II symptoms were associated with older age, more prominent imaging abnormalities, and MYH7 variants, suggesting both phenotype and genotype contribute to disease manifestations. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01912534.

Background: Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is believed to represent dense replacement fibrosis. It is seen in ≈60% of adult patients with hypertrophic cardiomyopathy (HCM). However, the prevalence of LGE in children and adolescents with HCM is not well established. In addition, longitudinal studies describing the development and evolution of LGE in pediatric HCM are lacking. This study assesses the prevalence, progression, and clinical correlations of LGE in children and adolescents with, or genetically predisposed to, HCM. Methods: CMR scans from 195 patients ≤21 years of age were analyzed in an observational, retrospective study, including 155 patients with overt HCM and 40 sarcomere mutation carriers without left ventricular (LV) hypertrophy. The extent of LGE was quantified by measuring regions with signal intensity >6 SD above nulled remote myocardium. Results: Patients were 14.3±4.5 years of age at baseline and 68% were male. LGE was present in 70 (46%) patients with overt HCM (median extent, 3.3%; interquartile range, 0.8–7.1%), but absent in mutation carriers without LV hypertrophy. Thirty-one patients had >1 CMR (median interval between studies, 2.4 years; interquartile range, 1.5–3.2 years). LGE was detected in 13 patients (42%) at baseline and in 16 patients (52%) at follow-up CMR. The median extent of LGE increased by 2.4 g/y (range, 0–13.2 g/y) from 2.9% (interquartile range, 0.8–3.2%) of LV mass to 4.3% (interquartile range, 2.9–6.8%) ( P =0.02). In addition to LGE, LV mass and left atrial volume, indexed to body surface area, and z score for LV mass, as well, increased significantly from first to most recent CMR. Conclusions: LGE was present in 46% of children and adolescents with overt HCM, in contrast to ≈60% typically reported in adult HCM. In the subset of patients with serial imaging, statistically significant increases in LGE, LV mass, and left atrial size were detected over 2.5 years, indicating disease progression over time. Further prospective studies are required to confirm these findings and to better understand the clinical implications of LGE in pediatric HCM.

AimsArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease and presymptomatic screening of relatives is recommended. In 2010, the Task Force Criteria (TFC2010) introduced specific diagnostic imaging parameters. The aim of the study was to evaluate the diagnostic yield of family screening and the value of different diagnostic modalities.Methods and resultsFamily evaluation, including cardiac magnetic resonance (CMR), is routinely offered to ARVC relatives at our institution. We retrospectively registered baseline characteristics, symptomatology, and results of non-invasive examinations from 2010 to 2016 and assessed the findings according to TFC2010. A total of 286 relatives (150 females; age 12–76 years; 251 first-degree) were included. A total of 103 (36%) individuals reported cardiovascular symptoms. The non-invasive workup showed that 101 (35%) relatives had ≥1 positive parameter on signal-averaged electrocardiogram (ECG), 40 (14%) had abnormal findings on Holter monitoring, 36 (13%) fulfilled an ECG criterion, six (2%) fulfilled CMR criteria, and echocardiographic abnormalities was seen in one (0.3%) relative. In total, 21 (7% overall; 13% among gene-positive subgroup) relatives were diagnosed with ARVC and 78 (27% overall; 49% among gene-positive subgroup) with borderline ARVC based on the combined non-invasive evaluations. Family history and electrical investigations alone diagnosed 20 out of 21 (95%) ARVC cases and 73 out of 78 (94%) borderline cases.ConclusionConsecutive evaluation of ARVC relatives diagnosed 7% with definite and 27% with borderline ARVC according to the TFC2010. Screening relatives for electrical abnormalities with 12 lead ECG, signal-averaged ECG, and Holter monitoring was more sensitive than imaging modalities.

Background Patients with nonischemic systolic heart failure are at an increased risk of sudden cardiac death, but more discriminating tools are needed to identify those patients likely to benefit from implantable cardioverter-defibrillator (ICD) implantation. Whether right ventricular (RV) ejection fraction (RVEF) can identify patients with nonischemic systolic heart failure more likely to benefit from ICD implantation is not yet known. Methods In this post hoc analysis of the DANISH trial (Danish Study to Assess the Efficacy of ICDs in Patients with Nonischemic Systolic Heart Failure on Mortality), patients with nonischemic systolic heart failure randomized to ICD or control underwent cardiovascular magnetic resonance. RV systolic dysfunction was defined as RVEF ≤45%. Cox regression assessed the effects of RV function and ICD implantation on all-cause mortality, sudden cardiac death, and cardiovascular death. Results Overall, 239 patients had interpretable images of RV volume. Median RVEF was 51%, RV systolic dysfunction was present in 75 (31%) patients, and 55 (23%) patients died. RVEF was an independent predictor of all-cause mortality, hazards ratio 1.34 per 10% absolute decrease in RVEF (95% CI, 1.05–1.70), P =0.02. There was a statistically significant interaction between RVEF and the effect of ICD implantation ( P =0.001). ICD implantation significantly reduced all-cause mortality in patients with RV systolic dysfunction, hazards ratio 0.41 (95% CI, 0.17–0.97), P =0.04 but not in patients without RV systolic dysfunction, hazards ratio 1.87 (95% CI, 0.85–3.92), P =0.12, ( P =0.01 for the difference in effect of ICD between RV groups). Conclusions In this post hoc analysis of the DANISH trial, ICD therapy was associated with survival benefit in patients with biventricular heart failure. These findings need confirmation in a prospective study. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00542945.

The aim of this study was to investigate the grading of diastolic dysfunction (DD) in relation to hemodialysis in patients with end stage renal disease (ESRD) on hemodialysis (HD) Cardiovascular disease is prevalent in patients with ESRD and accounts for significant morbidity and mortality. Left ventricular hypertrophy (LVH) is common in ESRD but little is known about the impact of HD on currently recommended grading schemes for DD. Comprehensive echocardiographic data was obtained in consecutive patients with ESRD before (n = 247) and immediately after (n = 239) standard HD regimen. Grading of DD was performed according to current recommendations both pre- and post HD. Prior to HD, DD was classified as present in 83 patients (34%), indeterminate in 51 patients (21%) and absent in 113 patients (45%). Patients with DD at baseline compared to those without were older [67.3 years (13.1) vs. 63.2 (14.3), p = 0.037], were more likely to have diabetic- or hypertensive ESRD (43.4% vs. 35.4%, p = ns) and LVMi was significantly higher [119 g/cm2 (27.5) vs. 103 g/cm2 (24.3), p

The Copenhagen Baby Heart Study (CBHS) is a population-based cohort study of neonates (N = 25,000), including echocardiography. Echocardiography in neonates is mainly focused on congenital heart disease (CHD), whereas general aspects of cardiac dimensions and function in neonates without CHD remain to be further addressed.This study was conducted to assess the reliability of neonatal echocardiography and validity of echocardiographic methods used in the CBHS.Reliability and agreement were tested for two-dimensional (2D), M-mode, spectral Doppler, and tissue velocity echocardiography for the following. (1) Measurements: seven sonographers independently performed two measurement rounds: (a) measurement of the same 50 echocardiograms (n = 350 echocardiograms measured) and (b) repeated measurement of 25 of the 50 echocardiograms (n = 175 echocardiograms measured). (2) Acquisition: four sonographers independently performed two rounds of echocardiographic acquisition and subsequent measurement of the same 22 neonates (n = 176 acquisitions and measures). Intra- and interobserver variabilities were assessed by determinations of coefficient of variation (CV), intraclass correlation coefficient (ICC), Bland-Altman plot, and 95% limits of agreement.(1) Measurements: we found intra- and interobserver ICC ≥ 0.67 for 2D parameters, except for left ventricular (LV) wall thicknesses and LV diameter (interobserver); ICC ≥ 0.84 for tricuspid annular plane systolic excursion (TAPSE); ICC ≥ 0.93 for pulsed-wave Doppler (PW); ICC ≥ 0.84 for continuous-wave Doppler; and ICC ≥ 0.87 for tissue velocity parameters. We found CV15% for all parameters except LV wall thicknesses. (2) Acquisition: we found intra- and interobserver ICC ≥ 0.69 for 2D parameters, except for LV wall thicknesses, aortic valve annulus (interobserver), and LV end-systolic diameter (interobserver); ICC = 0.45-0.49 for TAPSE; ICC = 0.48-0.64 for PW; and ICC ≥ 0.70 for continuous wave. We found CV15% for all parameters.Reliability of echocardiographic measurements and acquisition of cardiac dimensions and function were good for most parameters but lower for TAPSE (acquisition) and PW Doppler (acquisition) and poor for LV wall thicknesses. In general, echocardiography of cardiac dimensions and function in the neonate is reliable.