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To delineate the impact of diabetes mellitus (DM) on the development of cardiovascular diseases in a community population. Cross-sectional survey of residents randomly selected through the Rochester Epidemiology Project, 45 years or older, of Olmsted County as of June 1, 1997, through September 30, 2000. Responders (2042) underwent assessment of systolic and diastolic function using echocardiography. The current analyses included all participants with DM and were compared with a group of participants without DM matched 1:2 for age, sex, hypertension, and coronary artery disease. Baseline characteristics and laboratory and echocardiography findings between groups were compared along with rates of mortality due to various cardiovascular conditions. We identified 116 participants with DM and 232 matched participants without DM. Those with DM had a higher body mass index and plasma insulin and serum glucose levels. Although left ventricular ejection fractions were similar, E/e' ratio (9.7 vs 8.5; P=.001) was higher in DM vs non-DM. During a follow-up of 10.8 (interquartile range, 7.8-11.7) years, participants with DM had a higher incidence of heart failure (HF); hazard ratio, 2.1; 95% confidence limits, 1.2-3.6; P=.01) and 10-year Kaplan-Meier rate of 21% (22 of 116) vs 12% (24 of 232) compared with those without DM. We also examined the subgroup of participants without diastolic dysfunction. In this subgroup, those with DM had an increased risk for HF; hazard ratio, 2.5; 95% confidence limits, 1.0-6.3; P=.04). In this cohort, participants with DM have an increased incidence of HF over a 10-year follow-up period even in the absence of underlying diastolic dysfunction. These findings suggest that DM is an independent risk factor for the development of HF and supports the concept of DM cardiomyopathy.

Summary Background c-kit-positive, lineage-negative cardiac stem cells (CSCs) improve post-infarction left ventricular (LV) dysfunction when administered to animals. We undertook a phase 1 trial (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy [SCIPIO]) of autologous CSCs for the treatment of heart failure resulting from ischaemic heart disease. Methods In stage A of the SCIPIO trial, patients with post-infarction LV dysfunction (ejection fraction [EF] ≤40%) before coronary artery bypass grafting were consecutively enrolled in the treatment and control groups. In stage B, patients were randomly assigned to the treatment or control group in a 2:3 ratio by use of a computer-generated block randomisation scheme. 1 million autologous CSCs were administered by intracoronary infusion at a mean of 113 days (SE 4) after surgery; controls were not given any treatment. Although the study was open label, the echocardiographic analyses were masked to group assignment. The primary endpoint was short-term safety of CSCs and the secondary endpoint was efficacy. A per-protocol analysis was used. This study is registered with ClinicalTrials.gov , number NCT00474461. Findings This study is still in progress. 16 patients were assigned to the treatment group and seven to the control group; no CSC-related adverse effects were reported. In 14 CSC-treated patients who were analysed, LVEF increased from 30·3% (SE 1·9) before CSC infusion to 38·5% (2·8) at 4 months after infusion (p=0·001). By contrast, in seven control patients, during the corresponding time interval, LVEF did not change (30·1% [2·4] at 4 months after CABG vs 30·2% [2·5] at 8 months after CABG). Importantly, the salubrious effects of CSCs were even more pronounced at 1 year in eight patients (eg, LVEF increased by 12·3 ejection fraction units [2·1] vs baseline, p=0·0007). In the seven treated patients in whom cardiac MRI could be done, infarct size decreased from 32·6 g (6·3) by 7·8 g (1·7; 24%) at 4 months (p=0·004) and 9·8 g (3·5; 30%) at 1 year (p=0·04). Interpretation These initial results in patients are very encouraging. They suggest that intracoronary infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure after myocardial infarction, and warrant further, larger, phase 2 studies. Funding University of Louisville Research Foundation and National Institutes of Health.

Tissue Doppler echocardiography (TDI) is a convenient method to detect cardiac dysfunction in the infants of diabetic mothers (IDMs). Umbilical cord serum insulin-like growth factor-1 (IGF-1) is known to be higher in IDMs. We aimed to determine whether there is a relation between diastolic functions examined by TDI and cord serum IGF-1 levels of IDMs. Cord serum IGF-1 levels of 32 IDMs and 22 healthy infants were measured. The cardiac functions of the infants were evaluated by M-Mode and TDI. For statistical analysis, Mann–Whitney U and Spearman correlation tests were used for continuous variables, and the chi-square test was used for categorical variables. The cord serum IGF-1 levels of the IDMs were higher ( p  = 0.000). The left ventricle (LV) e', LVa', LV e'/a', and LV Tei index, indicating left ventricular diastolic dysfunction in IDMs, were detected (LV e' p  = 0.016; LV a' p  = 0.003; LV e'/ a' p  = 0.000; LV Tei index p  = 0.023). IDMs’ cord serum IGF-1 levels were found weakly correlated with the interventricular septum (IVS) and left ventricle posterior wall (LVPW) thicknesses in M-Mode and LV e' and LV e'/a' in TDI (IVS r  = 0.357, p  = 0.008; LVPW r  = 0.289, p  = 0.034; LV e' r  = 0.297, p  = 0.029; LV e'/ a' r  = 0.031, p  = 0.014). Conclusion : To our knowledge, this is the first study to examine the relationship between cord serum IGF-1 levels and diastolic functions of IDMs assessed by TDI. A weak correlation was found between IGF-1 levels and IVS and LVPW thicknesses in M-Mode and LV e' and LV e'/a' parameters in TDI, revealing diastolic dysfunction in IDMs. What is Known: • The umbilical cord blood serum IGF-1 level of IDMs is higher than in infants of healthy mothers. • Diastolic dysfunction is a well-studied and frequently observed consequence in IDMs. What is New: • This is the first study to examine the relationship between cord serum IGF-1 levels and diastolic functions of IDMs assessed by TDI. • A weak correlation was detected between the median cord serum IGF-1 level of IDMs and the median values of IVS, LVPW, LV e', LV a', LV e'/a' ratio.

RationaleDespite a significant association between obesity hypoventilation syndrome (OHS) and cardiac dysfunction, no randomised trials have assessed the impact of non-invasive ventilation (NIV) or CPAP on cardiac structure and function assessed by echocardiography.ObjectivesWe performed a secondary analysis of the data from the largest multicentre randomised controlled trial of OHS (Pickwick project, n=221) to determine the comparative efficacy of 2 months of NIV (n=71), CPAP (n=80) and lifestyle modification (control group, n=70) on structural and functional echocardiographic changes.MethodsConventional transthoracic two-dimensional and Doppler echocardiograms were obtained at baseline and after 2 months. Echocardiographers at each site were blinded to the treatment arms. Statistical analysis was performed using intention-to-treat analysis.ResultsAt baseline, 55% of patients had pulmonary hypertension and 51% had evidence of left ventricular hypertrophy. Treatment with NIV, but not CPAP, lowered systolic pulmonary artery pressure (−3.4 mm Hg, 95% CI −5.3 to –1.5; adjusted P=0.025 vs control and P=0.033 vs CPAP). The degree of improvement in systolic pulmonary artery pressure was greater in patients treated with NIV who had pulmonary hypertension at baseline (−6.4 mm Hg, 95% CI −9 to –3.8). Only NIV therapy decreased left ventricular hypertrophy with a significant reduction in left ventricular mass index (−5.7 g/m2; 95% CI −11.0 to –4.4). After adjusted analysis, NIV was superior to control group in improving left ventricular mass index (P=0.015). Only treatment with NIV led to a significant improvement in 6 min walk distance (32 m; 95% CI 19 to 46).ConclusionIn patients with OHS, medium-term treatment with NIV is more effective than CPAP and lifestyle modification in improving pulmonary hypertension, left ventricular hypertrophy and functional outcomes. Long-term studies are needed to confirm these results.Trial registration numberPre-results, NCT01405976 (https://clinicaltrials.gov/).

Cardiac output (CO) is routinely assessed by pulsed-wave Doppler echocardiography, yet reference values in adults are lacking. We aim to establish normative values of CO and cardiac index (CI) by pulsed-wave Doppler-echocardiography and to analyze their relation with gender and age in nonobese and obese adults. We included 4,040 adults (mean age: 55 years, 53% women, 950 obese [body mass index ≥30 kg/m²]) with normal blood pressure, no history of cardiovascular disease, and normal transthoracic echocardiography. Normative reference CO and CI values for were calculated in 3,090 nonobese patients by quantile regression. CO normal limits were lower in females than in males (lower limit: 3.3 vs 3.5 L/min, upper limit: 7.3 vs 8.2 L/min). CI normal limits were identical for both genders (lower limit: 1.9 L/min/m², upper limit: 4.3 L/min/m²). Although the relation of CO to age was weak and observed only in women, CI of both genders was not influenced by age. CO of obese patients was significantly greater than that of their nonobese counterparts. CI of obese patients was not influenced by age and gender and was not significantly different than that of nonobese patients (lower limit 1.8 L/min/m², upper limit 4.1 L/min/m² for both genders). In conclusion, in a large adult population we establish normative reference values for CO and CI measured by Doppler-echocardiography. CI is a remarkably stable parameter that is not influenced by age, gender, and body size and should be used to define low- and high-output states.

Taking into account the complexity and limitations of clinical assessment in hypertrophic cardiomyopathy (HCM), imaging techniques play an essential role in the evaluation of patients with this disease. Thus, in HCM patients, imaging provides solutions for most clinical needs, from diagnosis to prognosis and risk stratification, from anatomical and functional assessment to ischaemia detection, from metabolic evaluation to monitoring of treatment modalities, from staging and clinical profiles to follow-up, and from family screening and preclinical diagnosis to differential diagnosis. Accordingly, a multimodality imaging (MMI) approach (including echocardiography, cardiac magnetic resonance, cardiac computed tomography, and cardiac nuclear imaging) is encouraged in the assessment of these patients. The choice of which technique to use should be based on a broad perspective and expert knowledge of what each technique has to offer, including its specific advantages and disadvantages. Experts in different imaging techniques should collaborate and the different methods should be seen as complementary, not as competitors. Each test must be selected in an integrated and rational way in order to provide clear answers to specific clinical questions and problems, trying to avoid redundant and duplicated information, taking into account its availability, benefits, risks, and cost.

In patients with severe mitral regurgitation (MR) referred for cardiac surgery, left atrial (LA) remodeling and enlargement are accompanied by mechanical stress, mediated cellular hypertrophy, and interstitial fibrosis that finally lead to LA failure. Speckle tracking echocardiography is a novel non–Doppler-based method that allows an objective quantification of LA myocardial deformation, becoming useful for LA functional analysis. We conducted a study to evaluate the relation between the traditional and novel atrial indexes and the extent of ultrastructural alterations, obtained from patients with severe MR who were undergoing surgical correction of the valvular disease. The study population included 46 patients with severe MR, referred to our echocardiographic laboratory for a diagnostic examination before cardiac surgery. The global peak atrial longitudinal strain (PALS) was measured in all subjects by averaging all atrial segments. LA tissue samples were obtained from all patients. Masson's trichrome staining was performed to assess the extent of the fibrosis. The LA endocardial thickness was measured. A close negative correlation between the global PALS and grade of LA myocardial fibrosis was found (r = −0.82, p <0.0001), with poorer correlations for the LA indexed volume (r = 0.51, p = 0.01), LA ejection fraction (r = 0.61, p = 0.005), and E/E′ ratio (0.14, p = NS). Of these indexes, global PALS showed the best diagnostic accuracy to detect LA fibrosis (area under the curve 0.89), and it appears to be a strong and independent predictor of LA fibrosis. Furthermore, we also demonstrated an inverse correlation between the global PALS and LA endocardial thickness (r = −0.66, p = 0.0001). In conclusion, in patients with severe MR referred for cardiac surgery, impairment of LA longitudinal deformation, as assessed by the global PALS, correlated strongly with the extent of LA fibrosis and remodeling.

ObjectiveThe decision to perform percutaneous mitral commissurotomy (PMC) on asymptomatic patients requires careful weighing of the potential benefits against the risks of PMC, and we conducted a multicentre, randomised trial to compare long-term outcomes of early PMC and conventional treatment in asymptomatic, severe mitral stenosis (MS).MethodsWe randomly assigned asymptomatic patients with severe MS (defined as mitral valve area between 1.0 and 1.5 cm2) to early PMC (84 patients) or to conventional treatment (83 patients). The primary endpoint was a composite of major cardiovascular events, including PMC-related complications, cardiovascular mortality, cerebral infarction and systemic thromboembolic events. The secondary endpoints were death from any cause and mitral valve (MV) replacement during follow-up.ResultsIn the early PMC group, there were no PMC-related complications. During the median follow-up of 6.4 years, the composite primary endpoint occurred in seven patients in the early PMC group (8.3%) and in nine patients in the conventional treatment group (10.8%) (HR 0.77; 95% CI 0.29 to 2.07; p=0.61). Death from any cause occurred in four patients in the early PMC group (4.8%) and three patients in the conventional treatment group (3.6%) (HR 1.30; 95% CI 0.29 to 5.77). Ten patients (11.9%) in the early PMC group and 17 patients (20.5%) in the conventional treatment group underwent MV replacement (HR 0.59; 95% CI 0.27 to 1.29).ConclusionsCompared with conventional treatment, early PMC did not significantly reduce the incidence of cardiovascular events among asymptomatic patients with severe MS during the median follow-up of 6 years.Trial registration number NCT01406353.

ObjectiveWe hypothesised that abnormal global longitudinal strain (GLS) would predict outcome in hypertrophic cardiomyopathy (HCM) better than current echocardiographic measures.MethodsRetrospective analysis of risk markers in relation to outcomes in 472 patients with HCM at a single tertiary institution (2006–2012). Exclusion criteria were left ventricular (LV) hypertrophy of other origin, patients in atrial fibrillation, lost to follow-up and insufficient image quality to perform strain analysis. Standardised echocardiogram recordings were reviewed and standard variables and LV GLS were measured. The primary end-point included all cardiac deaths, appropriate defibrillator shocks and heart failure (HF) admissions. The secondary end-point was death by HF and admissions related to HF.ResultsMean age was 50.0±15.0 years; 322 (68%) were men. At a median of 4.3 years (IQR 0.1–7.8) follow-up, 21 (4.4%) patients experienced cardiovascular death: 6 (1.3%) died from HF, 13 (2.7%) had sudden cardiac death and 2 (0.4%) died secondary to stroke. Four (0.8%) patients experienced appropriate defibrillator shock, and 13 (2.7%) were admitted for HF. On multivariate Fine–Gray proportional hazard analyses, GLS was significantly associated with the primary end-point (HR=0.90, 95% CI 0.83 to 0.98, p=0.018) independently of age, maximal provoked LV outflow-tract gradient and LV end-systolic volume. Moreover, GLS was particularly associated with the secondary end-point (HR=0.82, 95% CI 0.75 to 0.90, p<0.0001) independently of age, previous atrial fibrillation, New York Heart Association (NYHA) class III–IV, LV end-systolic volume, E/E′, and outflow-tract gradient. Survival curves confirmed that GLS was associated with HF events (GLS <15.6%, p=0.0035).ConclusionsIn patients with HCM, reduced GLS is an independent factor associated with poor cardiac outcomes, and particularly HF outcomes.