Advanced Diastolic Dysfunction Research Articles

Diagnostic delay in wild type transthyretin cardiac amyloidosis – A clinical challenge

AimTo determine the diagnostic delay in patients with wild-type transthyretin cardiac amyloiodosis (ATTRwt). To determine the clinical and echocardiogtraphic characteristics of patients with an early and a late diagnosis and to study the suspected diagnoses and identification of diagnostic “red flags” before the ATTRwt diagnosis was established. MethodsIn 50 consecutive patients with ATTRwt diagnosed from 2017 to 2019, clinical and echocardiographic patient characteristics were investigated based on electronic patient charts and echocardiographic database review at Aarhus University Hospital, Denmark. ResultsThe median diagnostic delay was 13 months (2–47 months) and a diagnostic delay above 3 months was associated with more advanced symptoms and left ventricular (LV) diastolic dysfunction at the time of the diagnosis. Thirty patients (60%) were investigated for at least two non-ATTRwt diagnoses during the time period from the first cardiac examination to the time of the confirmed diagnosis. ATTR red flags were significantly less used in patients with the longest diagnostic delay (p < 0.001). Abormal LV global longitudinal strain (LV-GLS < 18%) and apical sparring ratio (APSR ≥ 1.5) were present in 96% and 94% of the ATTRwt patients, respectively. ConclusionThe diagnostic delay in ATTRwt was substantial and a prolonged diagnostic delay was associated with more advanced symptoms and LV diastolic dysfunction at the time of the diagnosis. Established ATTR red flags are poorly utilized in the diagnostic process. Echocardiographic analysis of LV-GLS and APSR contributes significantly to the evaluation of LV myocardial performance and helps raise the suspicion of ATTRwt.

The Association between Left Ventricular Diastolic Dysfunction and Myocardial Scar and Their Collective Impact on All-Cause Mortality

Left ventricular diastolic dysfunction (DD) and myocardial scar are important contributors to cardiovascular morbidity and mortality. The aim of this study was to test the hypothesis that myocardial scar is a substrate of DD and that collectively they contribute to increased risk for all-cause mortality. The study included 607 consecutive patients who underwent echocardiography and cardiac magnetic resonance imaging within 1week. DD was assessed by echocardiography according to the contemporary guidelines and myocardial scar by late gadolinium enhancement (LGE). All-cause mortality was the main outcome. Scar prevalence was significantly higher comparing no DD with mild and advanced DD (25%, 61%, and 80%, respectively; P<.001), and scar burden was greater by semiquantitative LGE scores (1.4±3.4, 4.8±6.3, and 6.8±8.8, respectively; P<.001). After 10 years of follow-up, 50 patients (8.2%) had died. The mortality incidence was significantly higher comparing no DD with mild and advanced DD (2.5, 17.3, and 55.7 deaths per 1,000 person-years, respectively; P<.001). It was also higher in patients with higher LGE scores (4.3, 22.7, and 35.2 deaths per 1,000 person-years in groups with LGE scores of 0, 1-6, and ≥7, respectively; P<.001). The risk for death was higher among patients with both DD and scar. The additive interaction of DD and scar for mortality was significant (P<.001). In the multivariate Cox proportional-hazards analysis, DD and scar were associated with mortality (P<.001). There is a strong link between the echocardiographic findings of DD and the morphologic changes of myocardial tissue. DD assessed according to contemporary guidelines effectively differentiates mortality risk. The additive interaction of DD and scar on mortality risk highlights the pivotal role of myocardial tissue characterization in patients with DD.

Preoperative echocardiographic evaluation of cardiac systolic and diastolic function in liver transplant recipients with diabetes mellitus: a propensity-score matched analysis.

BackgroundDiabetes mellitus (DM) increases risk of heart failure. It has been shown that diabetes leads to DM-cardiomyopathy, characterized by systolic and diastolic dysfunction. Pre-transplant diastolic dysfunction, has been associated with poor graft outcome and mortality. We assessed the hypothesis that end-stage liver disease (ESLD) patients with diabetes (DM-ESLD), have more advanced cardiac systolic and diastolic dysfunction, compared to ESLD patients without diabetes (Non DM-ESLD).MethodsWe retrospectively evaluated preoperative echocardiography of 1,319 consecutive liver transplant recipients (1,007 Non DM-ESLD vs. 312 DM-ESLD [23.7%]) January 2012–May 2016. Systolic and diastolic indices, such as left ventricular ejection fraction, transmital E/A ratio, tissue doppler s’, e’ velocity, and E/e’ ratio (index of left ventricular end-diastolic pressure), were compared using 1:2 propensity-score matching.ResultsDM-ESLD patients showed no differences in systolic indices of left ventricular ejection fraction and s’ velocity, whereas diastolic indices of E/A ratio ≤ 1 (49.0% vs. 40.2% P = 0.014), e’ velocity (median = 7.0 vs. 7.4 cm/s, P < 0.001) and E/e’ ratio (10.9 ± 3.2 vs. 10.1 ± 3.0, P < 0.001), showed worse diastolic function compare with Non DM-ESLD patients, respectively.ConclusionsDM-ESLD patients suffer higher degree of diastolic dysfunction compared with Non DM-ESLD patients. Based on this, careful preoperative screening for diastolic dysfunction in DM-ESLD patients is encouraged, because poor transplant outcomes have been noted in patients with preoperative diastolic dysfunction.

P2437Screening for cardiac relaxation abnormalities using surface ECG wavelets for identifying high-risk cardiac phenotypic abnormalities

Abstract Background The impairment of myocardial relaxation is a strong predictor of all-cause mortality and has been proposed to be a potential tool for cardiovascular (CV) risk stratification. We investigated a novel signal-processed electrocardiography (spECG) technique to extract the features of abnormal myocardial relaxation as a screening tool to identify high-risk CV patients. Methods Time–frequency-energy features extracted from continuous wavelet-transformed spECG (Fig. A) were obtained in 1,006 cases. A machine learning model was trained for predicting abnormal myocardial relaxation as a screening tool for detecting high-risk CV patients. High-risk CV phenotype was defined as presence of LV hypertrophy, advanced LV diastolic dysfunction (grade 2 or 3), LV ejection fraction &lt;50%, and/or significant valvular heart disease. Results After training with 5-fold cross validation using data from 810 patients, the machine learning model when tested in an independent hold-out validation set of 180 cases, showed an area under receiver-operating characteristic curve (AUC) of 0.83 (p&lt;0.001) for prediction of myocardial relaxation impairment (Fig. B). A prediction of abnormal relaxation was associated with older patients (64±11 vs. 45±16 years old, p&lt;0.001) with a higher prevalence of coronary artery disease (23% vs. 7%, p=0.004), hypertension (70% vs. 40%, p&lt;0.001), and diabetes (30% vs. 9%, p=0.001). Furthermore, a prediction of abnormal myocardial relaxation was associated with increased likelihood of high-risk CV phenotypes (Odds ratio: 3.93, p&lt;0.001) including LV hypertrophy (Odds ratio: 2.62, p=0.028), advanced LV diastolic dysfunction (Odds ratio: 11.4, p=0.020), and LV ejection fraction &lt;50% (Odds ratio 10.5, p=0.025). Age and gender modified the prediction of abnormal relaxation with higher diagnostic value seen for patients under 60 years (Fig C, AUC: 0.88, p&lt;0.001) and in male patients (Fig D, AUC: 0.87, p&lt;0.001). The algorithm for abnormal relaxation also showed robust prediction of LV ejection fraction &lt;50% (Fig E, AUC: 0.91, p&lt;0.001) in male patients. spECG showed significant net reclassification improvement (0.47, p&lt;0.001) and integrated discrimination improvement (0.16, p&lt;0.001) over traditional surface ECG interpretation using Glasgow score for predicting abnormal relaxation and other high-risk phenotypic presentations. ROC curves Conclusion The spECG provided a robust prediction of abnormal myocardial relaxation and may be a valuable screening strategy for early detection of high-risk cardiac structural and functional abnormalities.

P1248Characteristics and clinical significance of right ventricular involvement in patients with hypertrophic cardiomyopathy

Abstract Background A few studies have demonstrated bi-ventricular hypertrophy in hypertrophic cardiomyopathy (HCM). However, clinical significance of HCM with right ventricular (RV) involvement has not been fully established. Therefore, we aimed to investigate the structural characteristics and clinical significance of RV hypertrophy in patients with HCM. Methods In a single center, large HCM registry, 256 patients with HCM who underwent both cardiac magnetic resonance (CMR) and transthoracic echocardiography within 6 months were retrospectively analyzed. RV involvement was defined as increased RV wall thickness &gt;7 mm on CMR in any segments of RV free wall and apex. Patients who had evidence of significant RV pressure overload (RV systolic pressure &gt;50mmHg) or had undergone septal myectomy were excluded. Cardiovascular outcomes were defined as the composite of cardiovascular death and hospitalization for cardiovascular disease. Results Among 256 patients, 41 (16%) showed RV involvement. During follow-up period (median 1099 days), 32 cardiovascular outcomes (3 cardiovascular death and 29 cardiovascular hospitalization) were occurred. Patients with RV involvement showed a significantly higher left ventricular (LV) thickness (23.8±5.8 vs. 21.2±5.0 mm, p=0.004), more advanced diastolic dysfunction, and larger left atrial volume index (LAVI, 48.5±20.3 vs. 40.2±14.9 mm/m2, p=0.016) compared to those without RV involvement. In multivariate cox regression analysis, presence of RV involvement (HR: 4.21, 95% CI: 1.99–8.90, p&lt;0.001) and LV ejection fraction &lt;50% (HR: 4.29, 95% CI: 1.37–13.43, p=0.012) were independently associated with cardiovascular outcomes. The Kapan-Meier curve showed that there was a significant decrease in probability of cardiovascular outcomes-free survival in patients with RV involvement (p=0.007) after using 1:1 propensity score matching (n=82) to adjust for age, sex, LV ejection fraction, LV maximal wall thickness, LAVI, and RV systolic pressure than patients without RV involvement (Figure 1). Figure 1 Conclusion RV involvement in patients with HCM were not rare (16%). Patients with RV involvement showed more advanced LV structure and dysfunction, suggesting an indicator of severe HCM. RV involvement in HCM has clinical significance related to cardiovascular outcomes.

P911High rate of cardiac amyloidosis in elderly patients with aortic stenosis: clinical presentation before and after aortic valve intervention

Abstract Background Aortic Stenosis (AS) is the most common valvular heart disease in the Western world. Wild-type transthyretin amyloid (wtATTR) affects the heart, causing restrictive cardiomyopathy. Deposits can be found in up to 25% of individuals &gt;85 years of age at autopsy. Recently several reports showed a relatively high prevalence of transthyretin cardiac amyloidosis (TTR-CA) in patients with AS. Objectives The aim of this study was to examine the clinical effects of TTR-CA in patients who have undergone aortic valve replacement therapy and evaluate the outcome of the intervention. Methods We recruited patients who underwent surgical (AVR) or percutaneous (TAVI) aortic valve intervention between 2011 and 2018. The patients underwent a Tc99m-PYP scan using SPECT technology which has been shown to be valid for the diagnosis of TTR-CA. We reviewed patient files before (time point 1) and after intervention (time point 2) and at 2 years (time point 3) follow up, and collected data on hospitalizations, laboratory, and echocardiography. Results The study included 86 patients, mean age 78±6 years, 55% women. Twenty-nine (33%) participants were diagnosed as positive (VAS 2 and 3) for transthyretin cardiac amyloidosis.There were no differences in baseline characteristics between patients with and without TTR-CA in cardiovascular risk factors and co-morbidities, laboratory parameters and nutritional status. There were no differences in baseline echocardiographic parameters including valve gradients and left ventricular hypertrophy. However, the patients with TTR CA had more advanced diastolic dysfunction compared to patients without TTR CA (P=0.03) and higher pulmonary artery pressure (44±14.75mmhg vs 30.5±11.38mmhg, p=0.06). Before the intervention, patients with transthyretin cardiac amyloidosis had 3.26 times more hospitalizations due to heart failure as compared to patients in the negative group (p=0.01). After the intervention, diastolic function remained more severely affected in the positive group at all follow-up points compared to the negative group (p=0.05). Similar observations were seen in the measurements of pulmonary arterial pressure (p=0.019 at time 2 and p=0.015 at time 3). Consistent with the echocardiographic findings, patients with transthyretin cardiac amyloidosis had 2.84 times more hospitalizations after intervention for heart failure than patients in the negative group (p=0.02). Conclusions Co-existence of transthyretin cardiac amyloidosis and aortic stenosis in the older population is associated with a more severe clinical presentation and with more advanced clinical and echocardiographic signs of heart failure. Improvement after valvular intervention might be limited in terms of symptoms and hospitalizations in this subgroup. Acknowledgement/Funding None

Impact of diastolic dysfunction on long-term mortality and quality of life after transcatheter aortic valve replacement.

There is conflicting data as to whether diastolic dysfunction (DD) affects the prognosis of patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Consecutive patients undergoing TAVR underwent assessment of DD with preoperative echocardiography and NT-pro BNP. Long-term survival was ascertained every 6 months by clinic visits or phone. DD was graded according to the new American Society of Echocardiography recommendations. Health status was assessed at baseline and 30 days post-procedure using the KCCQ-12 questionnaire. Long-term survival was displayed using Kaplan-Meier curves according to NT-pro BNP levels and DD grades. We included 222 patients, mean age 78 (±8) years, median STS score 4 (interquartile range = 3-7), median follow-up time 385 days (IQR = 180-640). DD was absent in 25, Grade I in 13, Grade II in 74, Grade III in 24, and indeterminate in 86 patients. Advanced (Grades II-III) DD was associated with higher pre-procedural NT-pro BNP levels (p < .001), worse quality of life (p < .001) but similar surgical risk (p = .43). Advanced and indeterminate DD were associated with increased long-term mortality (25-28% vs. 5%, p = .02) and elevated NT-pro BNP levels (26.4% vs. 9.8%, p = .05). Improvements in quality of life measures were seen in all DD groups (median change in KCCQ score no or Grade I DD:14 [3-21] vs. Grades II-III DD: 15 [16-26; p = .37]). Preoperative NT-pro BNP levels and echocardiographic indices of indeterminate or advanced DD are associated with increased long-term mortality after TAVR but similar improvements in quality of life.

Prognostic impact of mitral L-wave in patients with hypertrophic cardiomyopathy without risk factors for sudden cardiac death.

Hypertrophic cardiomyopathy (HCM) with severe diastolic dysfunction is a major cause of heart failure and sudden cardiac death (SCD) associated with lethal arrhythmia. Although various risk factors for cardiac events have been reported in HCM patients, previous studies have reported that some HCM patients exhibit either no risk or a low risk of SCD experienced cardiac events. The mid-diastolic transmitral flow velocity curve (mitral L-wave) is an echocardiographic index of left ventricular compliance, and it has been reported as one of the parameters of advanced diastolic dysfunction assessed noninvasively. However, little is known about the association between the mitral L-wave and long-term clinical outcomes in HCM patients without SCD risk factors. Between July 2005 and February 2016, 112 patients were diagnosed with HCM and 96 patients without risk factors were enrolled. After excluding 3 patients whom we could not detect L-wave more than once, 93 patients (mean age 57.7 ± 13.1years, 33 females) were divided into the following two groups, according to the presence or absence of the mitral L-wave: Group L (+) (with the mitral L-wave) and Group L (-) (without the mitral L-wave). The correlations between the mitral L-wave and rates of cardiac events were investigated. The mitral L-wave was present in 14 (15.1%) patients [Group L]. During the follow-up period [4.7 (2.9-7.5) years], patients experienced 7 cardiac events. Kaplan-Meier survival analysis showed that the event-free rate was significantly lower in Group L (+) than in Group L (-) (log-rank P = 0.002). Additionally, in multivariate analysis, L-wave positivity was identified as independent predictors of cardiac events. Existence of the mitral L-wave can predict cardiac events, even in HCM patients without SCD risk factors.

Un análisis general de la prolisil-oxidasa circulante en pacientes no isquémicos con una insuficiencia cardiaca común con fracción de eyección conservada

Introduction and objectivesLysyl oxidase is overexpressed in the myocardium of patients with hypertensive cardiomyopathy. We aimed to explore whether patients with hypertensive-metabolic heart failure with preserved ejection fraction (HM-HFpEF) also have increased concentrations of circulating prolysyl oxidase (cpLOX) and its possible consequences. MethodsWe quantified cpLOX concentrations in 85 nonischemic patients with stage C, HM-HFpEF, and compared them with those of 51 healthy controls. We also assessed the correlations of cpLOX with myocardial stiffness parameters, collagen turnover products and fibrogenic cytokines, as well as the predictive value of plasma proenzyme levels at 1-year of follow-up. ResultsWe detected raised cpLOX values and found that they correlated with calculated E/E’ ratios and stiffness constants. The subgroup of patients with type I diastolic dysfunction showed a single negative correlation between cpLOX and B-type natriuretic peptide whereas patients with a restrictive diastolic pattern showed a strong correlation between cpLOX and galectin-3. Kaplan-Meier analysis revealed that cpLOX > 52.20 ng/mL slightly increased the risk of a fatal outcome (log-rank = 4.45; P = .034). When Cox regression was used, cpLOX was found to be a significant independent predictor of cardiovascular death or hospitalization due to the decompensation of HM-HFpEF (HR, 1.360; 95%CI, 1.126-1.638; P = .046). ConclusionsPatients with symptomatic HM-HFpEF show high cpLOX serum levels associated with restrictive diastolic filling indices. These levels represent a moderate risk factor for poor clinical outcome. Throughout the natural history of HM-HFpEF, we observed that cpLOX concentrations were initially negatively correlated with B-type natriuretic peptide but positively correlated with galectin-3 as advanced diastolic dysfunction developed.Full English text available from:www.revespcardiol.org/en

Ischaemic aetiology predicts exercise dyssynchrony in patients with heart failure with reduced ejection fraction.

Left ventricular (LV) dyssynchrony is common in patients with heart failure with reduced ejection fraction (HFREF). However, various conditions including exercise may alter its presence. LV dyssynchrony at exercise (ExDYS) has been associated with lower cardiac performance and exercise capacity but with higher cardiac resynchronization therapy (CRT) response. Therefore, understanding mechanisms underlying ExDYS may improve patient selection for CRT. To investigate for predictors of ExDYS among patients with HFREF and prolonged QRS duration. Consecutive patients with stable, chronic HF, LVEF<35%, sinus rhythm and QRS≥120ms were eligible. 2D echocardiography and tissue-Doppler were performed at rest and peak cyclo-ergometer exercise to assess LV systolic (LVEF) and diastolic function [mitral E-to-e'-wave velocities (E/e')] and dyssynchrony. Dyssynchrony was defined as a maximal difference between time-to-peak systolic velocities of≥65ms from opposing basal segments. We included 48 patients (aged 63.7±12.2, 81.3% male). Ischaemic aetiology (ICM) was present in 23 (47.9%). Dyssynchrony at rest (rDYS) was present in 32 (66.6%) patients, while ExDYS in 23 (47.9%). ExDYS correlated with ICM, lower LVEF and higher E/e' ratio. ICM remained significant predictor of ExDYS in multiple regression model (OR:4.3, 95%CI:1.2-15.7, p=003). On exercise, 19 (39.5%) patients changed the rDYS status. While, exercise-induced dyssynchronization was observed only in ICM patients, exercise-induced resynchronization was more likely in patients with lower rest E/e' ratio (OR:0.85, 95%CI:0.75-0.97, p=0.02). Ischaemic aetiology of HFREF is an important predictor of ExDYS. Restoration of LV synchronicity during exercise is more likely in patients with less advanced LV diastolic dysfunction.

Sex Differences at the Time of Myectomy in Hypertrophic Cardiomyopathy.

One of the first clinically detectable alterations in heart function in hypertrophic cardiomyopathy (HCM) is a decline in diastolic function. Diastolic dysfunction is caused by changes in intrinsic properties of cardiomyocytes or an increase in fibrosis. We investigated whether clinical and cellular parameters of diastolic function are different between male and female patients with HCM at the time of myectomy. Cardiac tissue from the interventricular septum of patients with HCM (27 women and 44 men) was obtained during myectomy preceded by echocardiography. At myectomy, female patients were 7 years older than male patients and showed more advanced diastolic dysfunction than men evident from significantly higher values for E/e' ratio, left ventricular filling pattern, tricuspid regurgitation velocity, and left atrial diameter indexed for body surface. Whereas most male patients (56%) showed mild (grade I) diastolic dysfunction, 50% of female patients showed grade III diastolic dysfunction. Passive tension in HCM cardiomyocytes was comparable with controls, and myofilament calcium sensitivity was higher in HCM compared with controls, but no sex differences were observed in myofilament function. In female patients with HCM, titin was more compliant, and more fibrosis was present compared with men. Differences between female and male patients with HCM remained significant after correction for age. Female patients with HCM are older at the time of myectomy and show greater impairment of diastolic function. Furthermore, left ventricular and left atrial remodeling is increased in women when corrected for body surface area. At a cellular level, HCM women showed increased compliant titin and a larger degree of interstitial fibrosis.

A Global Assessment of Circulating Prolysyl Oxidase in Nonischemic Patients With Garden-variety Heart Failure With Preserved Ejection Fraction

Introduction and objectivesLysyl oxidase is overexpressed in the myocardium of patients with hypertensive cardiomyopathy. We aimed to explore whether patients with hypertensive-metabolic heart failure with preserved ejection fraction (HM-HFpEF) also have increased concentrations of circulating prolysyl oxidase (cpLOX) and its possible consequences. MethodsWe quantified cpLOX concentrations in 85 nonischemic patients with stage C, HM-HFpEF, and compared them with those of 51 healthy controls. We also assessed the correlations of cpLOX with myocardial stiffness parameters, collagen turnover products and fibrogenic cytokines, as well as the predictive value of plasma proenzyme levels at 1-year of follow-up. ResultsWe detected raised cpLOX values and found that they correlated with calculated E/E’ ratios and stiffness constants. The subgroup of patients with type I diastolic dysfunction showed a single negative correlation between cpLOX and B-type natriuretic peptide whereas patients with a restrictive diastolic pattern showed a strong correlation between cpLOX and galectin-3. Kaplan-Meier analysis revealed that cpLOX > 52.20 ng/mL slightly increased the risk of a fatal outcome (log-rank = 4.45; P = .034). When Cox regression was used, cpLOX was found to be a significant independent predictor of cardiovascular death or hospitalization due to the decompensation of HM-HFpEF (HR, 1.360; 95%CI, 1.126-1.638; P = .046). ConclusionsPatients with symptomatic HM-HFpEF show high cpLOX serum levels associated with restrictive diastolic filling indices. These levels represent a moderate risk factor for poor clinical outcome. Throughout the natural history of HM-HFpEF, we observed that cpLOX concentrations were initially negatively correlated with B-type natriuretic peptide but positively correlated with galectin-3 as advanced diastolic dysfunction developed.

Deterioration of Deceleration Capacity of Heart Rate is Associated with Left Ventricular Hypertrophy in End-Stage Renal Disease Population.

Left ventricular hypertrophy (LVH) is prevalent in patients with end-stage renal disease (ESRD), and may be secondary to arterial stiffness and volume overload. It is unclear whether LVH is caused by autonomic nerve dysregulation (AND), a frequent condition in patients with ESRD that is characterized by sympathetic hyperactivity and vagal withdrawal. We hypothesized that AND estimated by heart rate variability (HRV) may be associated with LVH in patients with ESRD. We prospectively enrolled patients with ESRD undergoing hemodialysis. Cardiac function and LVH were assessed using echocardiography according to the recommendations of the American Society of Echocardiography. Holter recordings were used to quantify HRV and deceleration capacity (DC). Dataon comorbidities and medications, and serum markers were obtained. Logistic regression analysis was performed. Among the 281 included patients, 63% had LVH. The patients with LVH were older, had more comorbidities and advanced diastolic dysfunction than those without LVH. The root mean square of successive differences (rMSSD) (9.10 ± 5.44 versus 13.25 ± 8.61; p = 0.004) and DC (2.08 ± 1.90 versus 3.89 ± 1.45; p = 0.021) were lower in the patients with LVH than that in those without LVH. Multivariate regression analysis showed that hypertension, asymmetrical dimethylarginine (ADMA), advanced diastolic dysfunction grade, rMSSD, and DC were independently associated with LVH. Among these variables, DC and ADMA showed the highest diagnostic value for LVH with areas under curves of 0.701 and 0.751, respectively. AND is independently associated with LVH in patients with ESRD.

Subclinical left ventricular systolic and diastolic dysfunction in type 1 diabetic children and adolescents with good metabolic control.

Cardiac dysfunction is a well-known consequence of diabetes mellitus. This study was designed to assess whether type 1 diabetic children and adolescents with good metabolic control have early echocardiographic signs of subclinical left ventricular dysfunction and whether diabetes duration has any influence, using conventional and nonconventional echocardiographic tools. A total of 100 patients with type 1 diabetes mellitus and 80 gender- and age-matched healthy controls were included. The cases underwent standard conventional transthoracic echocardiography, tissue Doppler imaging, and two-dimensional speckle tracking echocardiography. None of the diabetic patients had signs of renal, retinal, or neurological complications of the disease, and all were good metabolic control (mean HbA1c <7.5%). There was no difference among groups in relation to age, sex, body mass index, and blood pressure. Conventional echocardiographic parameters were similar between diabetic and nondiabetic subjects except increased mitral valve peak A-wave and significantly lower mitral E/A ratio in diabetics. Diabetic patients had more advanced diastolic dysfunction with TDI analysis. In the diabetic group, left ventricular global longitudinal, circumferential, and radial strain and strain rate were significantly lower compared with the controls. There was a positive correlation between diabetes duration and cardiac dysfunction. The results of this study showed that the diabetic children and adolescents with good metabolic control had diastolic dysfunction when assessed with either conventional or tissue Doppler echocardiography. Also diabetic patients had subclinical LV systolic dysfunction with a normal LVEF which can be detected with 2D speckle tracking echocardiography.

Cardiovascular morphometry with high-resolution 3D magnetic resonance: First application to left ventricle diastolic dysfunction

In this study, an image-based morphometry toolset quantifying geometric descriptors of the left ventricle, aorta and their coupling is applied to investigate whether morphological information can differentiate between subjects affected by diastolic dysfunction (patient group) and their age-matched controls (control group). The ventriculo-aortic region of 20 total participants (10 per group) were segmented from high-resolution 3D magnetic resonance images, from the left ventricle to the descending aorta. Each geometry was divided into segments in correspondence of anatomical landmarks. The orientation of each segment was estimated by least-squares fitting of the respective centerline segment to a plane. Curvature and torsion of vessels’ centerlines were automatically extracted, and aortic arch was characterized in terms of height and width.Tilt angle between subsequent best-fit planes in the left ventricle and ascending aorta regions, curvature and cross-sectional area in the descending aorta resulted significantly different between patient and control groups (P-values< 0.05). Aortic volume (P = 0.04) and aortic arch width (P = 0.03) resulted significantly different between the two groups. The observed morphometric differences underlie differences in hemodynamics, by virtue of the influence of geometry on blood flow patterns.The present exploratory analysis does not determine if aortic geometric changes precede diastolic dysfunction, or vice versa. However, this study (1) underlines differences between healthy and diastolic dysfunction subjects, and (2) provides geometric parameters that might help to determine early aortic geometric alterations and potentially prevent evolution toward advanced diastolic dysfunction.

Atrial Fibrillation in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder with a spectrum of clinical manifestations. Patients with HCM are predisposed to developing atrial fibrillation (AF) due primarily to advanced diastolic dysfunction and left atrial (LA) dilatation and remodelling. Atrial fibrillation causes a progressive symptomatic and functional decline, as well as increased thromboembolic risk and mortality, particularly in the setting of rapid ventricular rates and left ventricular outflow tract (LVOT) obstruction. The mainstay of management of AF in HCM is a combination of non-pharmacological lifestyle and risk factor modification, long-term anticoagulation, and rhythm control with antiarrhythmic medications. There is a growing body of evidence indicating that an early and aggressive rhythm control strategy may result in more favourable outcomes.

Long-term outcome of patients with triphasic mitral flow with a mid-diastolic L wave: prognostic role of left atrial volume and N-terminal pro-brain natriuretic peptide.

A mid-diastolic L wave has been recognized as a marker of advanced left ventricular (LV) diastolic dysfunction. However, its prognostic implication is unclear. This study assessed long-term prognosis and independent predictors of adverse outcomes in patients with a mid-diastolic L wave. A total of 144 consecutive patients (mean age 63 ± 12 years, 88 female) with a mid-diastolic L wave of ≥0.2m/s and in sinus rhythm were identified. Patients with significant valvular heart disease, low LV ejection fraction and arrhythmias were excluded. Subjects were followed up for cardiovascular (CV) mortality and hospitalization for heart failure (HF). During follow-up for a median of 44 months (1-76), CV deaths and hospitalization for HF occurred in 41 (28%) patients. In multivariate Cox analysis, age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.11; p = 0.001), log N-terminal pro-brain natriuretic peptide (NT-proBNP)(HR 3.81; 95% CI 1.78-8.15; p = 0.001), and left atrial volume index (HR 1.02; 95% CI 1.01-1.04; p = 0.019) were independent predictors of adverse outcomes in patients with a mid-diastolic L wave. In a stepwise model, NT-proBNP showed an incremental prognostic value for prediction of adverse outcomes when added to the clinical and echocardiographic parameters (Chi square from 30.1 to 41.1, p < 0.001). Patients with a mid-diastolic L wave and clinical, biochemical, and echocardiographic evidence of advanced diastolic dysfunction showed poor long-term clinical outcome.

Impaired Myocardial Sympathetic Innervation Is Associated with Diastolic Dysfunction in Heart Failure with Preserved Ejection Fraction: 11C-Hydroxyephedrine PET Study.

Diastolic dysfunction is important in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Sympathetic nervous hyperactivity may contribute to the development of diastolic dysfunction. The aim of this study was to determine the relationship between myocardial sympathetic innervation quantified by 11C-hydroxyephedrine PET and diastolic dysfunction in HFpEF patients. Methods: Forty-one HFpEF patients having an echocardiographic left ventricular ejection fraction of 40% or greater and 12 age-matched volunteers without heart failure underwent the echocardiographic examination and 11C-hydroxyephedrine PET. Diastolic dysfunction was classified into grades 0-3 by Doppler echocardiography. Myocardial sympathetic innervation was quantified using the 11C-hydroxyephedrine retention index (RI). The coefficient of variation of 17-segment RIs was derived as a measure of heterogeneity in myocardial 11C-hydroxyephedrine uptake. Results: Grade 2-3 diastolic dysfunction (DD2-3) was found in 19 HFpEF patients (46%). They had a significantly lower global RI (0.075 ± 0.018 min-1) than volunteers (0.123 ± 0.028 min-1, P < 0.001) and HFpEF patients with grade 0-1 diastolic dysfunction (DD0-1) (0.092 ± 0.024 min-1, P = 0.046). HFpEF patients with DD2-3 had the largest coefficient of variation of 17-segment RIs of the 3 groups (18.4% ± 7.7% vs. 14.1% ± 4.7% in HFpEF patients with DD0-1, P = 0.042 for post hoc tests). In multivariate logistic regression analysis, a lower global RI (odds ratio, 0.66 per 0.01 min-1; 95% confidence interval, 0.38-0.99; P = 0.044) was independently associated with the presence of DD2-3 in HFpEF patients. Conclusion: Myocardial sympathetic innervation was impaired in HFpEF patients and was associated with the presence of advanced diastolic dysfunction in HFpEF.

Comparison of echocardiographic parameters between pre-clinical and clinical advanced diastolic dysfunction patients

BackgroundThe diagnosis of heart failure (HF) with preserved ejection fraction requires evidence of grade 2 or 3 (advanced) diastolic dysfunction (ADD), but many patients with ADD do not have clinical HF manifestations, hence termed pre-clinical diastolic dysfunction (PDD). The prevalence and characteristics of PDD in comparison to overt HF disease (clinical-ADD) are still debated. MethodsWe retrospectively analyzed 373 patients with LVEF≥45% and ADD in our echo-lab database. Exclusion criteria were acute coronary syndromes, ≥moderate valvular disease, cardiomyopathies or pericardial disease. Patients were divided into 2 groups according to the presence/absence of HF symptoms, namely PDD (n=249) and clinical-ADD (n=124). Demographic, clinical and echocardiographic parameters were compared between the groups. ResultsAge, gender and comorbidities were similar between groups, with only a higher body mass index and renal failure significantly more prevalent in the clinical-ADD patients. Neither LV mass nor the ADD severity was related to the presence of symptoms; lateral mitral E/E′ and pulmonary artery systolic pressure were significantly higher in clinical-ADD patients (14±5 vs. 12±4, p<0.05 and 40±13 vs. 36±11mmHg, p<0.05, respectively) and were the only parameters to correlate with the presence of symptoms of clinical-ADD in multivariable logistic regression (odds ratio=1.07 (CI 1.02–1.1, p=0.008) and 1.03 (CI 1.01–1.05, p=0.01), respectively). ConclusionsIn patients referred for an echocardiogram at a community cardiology center, PDD was twice as common as clinical-ADD. Hemodynamic parameters reflecting elevated filling and pulmonary pressures, rather than traditional comorbidities and/or classical structural abnormalities, were the only parameters related to the presence of HF symptoms.

Additional value of Galectin-3 to BNP in acute heart failure patients with preserved ejection fraction

BackgroundAlmost half of patients with acute heart failure have preserved ejection fraction (HFpEF). HFpEF is a diagnostic challenge using traditional investigation tools; Galectin-3 (Gal-3) is an emerging biomarker useful in individuals at risk for HF. The aim of our study is to analyse the relation and prognostic value of Gal-3, BNP and renal dysfunction in patients with HFpEF compared to patients with reduced ejection fraction (HFrEF). MethodsWe enrolled 98 patients with acute heart failure (AHF) and measured Gal-3, BNP, and estimated glomerular filtration rate (eGFR) within 12h of hospital admission. On the basis of echocardiographic findings we divided our sample into two groups: patients with HFrHF (ejection fraction<50%) or HFpEF (ejection fraction>50%). Patients were followed up at 6months. ResultsNo differences in Gal-3 levels were found in the two subgroups (HFrEF: 19.5±5.1ng/mL; HFpEF: 20.5±8.7, p=0.56). Gal-3 was inversely related to renal dysfunction (LogGal-3 vs eGFR: r=−0.30, p=0.01) but did not correlate with LogBNP levels (r=0.07, p=0.55). Gal-3 was associated with more advanced diastolic dysfunction in HFpEF (p=0.009). In addition LogGal-3 was related to diastolic LV stiffness (all patients: r=0.45, p<0.001; HFpEF: r=0.64, p<0.001). Cox regression analysis showed that LogGal-3>1.30 was related to poor outcome independently from renal dysfunction and other risk factors only in HFpEF (univariate HR 23.98 [3.03–89.45]; p<0.001). Adjusted for renal dysfunction (HR 16.32 [1.98–34.09]; p=0.009). ConclusionsGal-3 is not able to distinguish between HFrEF and HFpEF patients. However it is related to diastolic dysfunction severity and LV stiffness in HFpEF. Gal-3 demonstrates a prognostic role independently from renal dysfunction in subjects with HFpEF.