Apical two- and four-chamber views (A2C and A4C) and real-time 3D datasets (Toshiba Artida 4D System) obtained in 43 patients with a wide range of LV size and function were analysed to measure LV end-systolic and end-diastolic volumes (ESV and EDV) using 2D and 3D-STE techniques. Short-axis CMR images (Siemens 1.5T scanner) acquired on the same day were analysed to obtain ESV and EDV reference values using the method of disks approximation. Reproducibility of both STE techniques was assessed using repeated measurements. While 2D-STE correlated well with CMR (r: 0.72–0.88), it underestimated LV volumes with relatively large biases (10–30 mL) and wide limits of agreement (SD: 36–51 mL), with A2C-derived measurements being worse than A4C values. The 3D-STE measurements showed higher correlation with CMR (0.87–0.92), and importantly smaller biases (1–16 mL) and narrower limits of agreement (SD: 28–37 mL). In addition, 3D-STE showed lower inter- and intra-observer variability (11–14% and 12–13%), than 2D-STE (16–17% and 12–16%, respectively).

This is the first study to validate the new 3D-STE technique for LV volume measurements and demonstrate its superior accuracy and reproducibility over previously used 2D-STE technique.

Perioperative ECGs, creatinine kinase MB fraction, and cardiac troponin I (cTnI) were assessed in 545 primary CABG patients. None of the ECG criteria for myocardial injury predicted mortality or HLOS. However, post-operative day (POD) 1 cTnI levels independently predicted 5-year mortality (hazard ratio = 1.42; 95% CI 1.14–1.76 for each 10 µg/L increase; P = 0.009), while adjusting for baseline demographic characteristics and perioperative risk factors. Moreover, cTnI was the only biomarker that significantly improved the prediction of 5-year mortality estimated by the logistic Euroscore (P = 0.02). Furthermore, the predictive value of cTnI for 5-year mortality was replicated in a separately collected cohort of 1031 CABG patients using cardiac troponin T.

Electrocardiogram diagnosis of post-operative myocardial injury after CABG does not independently predict an increased risk of 5-year mortality or HLOS. Conversely, cTnI is independently associated with an increased risk of mortality and prolonged HLOS.

The T111I variant was genotyped in case–control studies of CHD nested within the Diet, Cancer, and Health study with 998 cases, Nurses’ Health Study with 241 cases, and Health Professionals Follow-up Study with 262 cases. The minor allele frequency in the combined pool of controls was 0.29. The T111I variant was not associated with HDL-C or any other lipid and lipoprotein measures. Compared with wildtype homozygotes, the pooled estimate for risk of CHD was 0.95 (0.85–1.06) per T111I allele.

Our analysis among healthy Caucasian men and women from three independent studies does not support an association between the T111I variant and HDL-C, other plasma lipids, or risk of CHD.

In 454 patients undergoing PCI, acetylcholine (10^–6 to 10^–4 M) was infused in a coronary segment without significant CAD. Changes in coronary diameter were measured and an intravascular ultrasound examination (IVUS) was performed. On top of statin therapy, patients were randomized in a double-blind fashion to placebo or nifedipine GITS 30–60 mg/day and followed for 18–24 months.

Blood pressure was lower on nifedipine than on placebo by 5.8/2.1 mmHg (P < 0.001) as was total and LDL cholesterol (4.8 mg/dL; P = 0.495), while HDL was higher (3.6 mg/dL; P = 0.026). In the most constricting segment, nifedipine reduced vasoconstriction to acetylcholine (14.0% vs. placebo 7.7%; P < 0.0088). The percentage change in plaque volume with nifedipine and placebo, respectively, was 1.0 and 1.9%, ns.

The ENCORE II trial demonstrates in a multi-centre setting that calcium channel blockade with nifedipine for up to 2 years improves coronary endothelial function on top of statin treatment, but did not show an effect of nifedipine on plaque volume.

The CAPTIM study included 840 patients managed in a pre-hospital setting within 6 h of an acute ST-segment elevation myocardial infarction. Patients were randomized to either a primary angioplasty (n = 421) or a pre-hospital fibrinolysis (rt-PA) with immediate transfer to a centre with interventional facilities (n = 419). Long-term follow-up was obtained in blinded fashion from 795 patients (94.6%). Using an intent-to-treat analysis, all-cause mortality at 5 years was 9.7% in the pre-hospital fibrinolysis group when compared with 12.6% in the primary angioplasty group [HR 0.75 (95% CI, 0.50–1.14); P = 0.18]. For patients included within 2 h, 5 year mortality was 5.8% in the pre-hospital fibrinolysis group when compared with 11.1% in the primary angioplasty group [HR 0.50 (95% CI, 0.25–0.97); P = 0.04], whereas it was, respectively, 14.5 and 14.4% in patients included after 2 h [HR 1.02, (95% CI 0.59–1.75), P = 0.92].

The 5-year follow-up is consistent with the 30-day outcomes of the trial, showing similar mortality for primary percutaneous coronary intervention and a policy of pre-hospital lysis followed by transfer to an interventional center. In addition, for patients treated within 2 h of symptom onset, 5-year mortality was lower with pre-hospital lysis.

All hearts were exposed to 30 min regional ischaemia followed by 120-(isolated hearts) or 180-(in situ hearts) min reperfusion. BAY-58 (1–50 nM) infused for 60 min starting 5 min before reperfusion significantly reduced infarction from 33.0 ± 3.2% in control isolated rabbit hearts to 9.5–12.7% (P < 0.05). In a more clinically relevant in situ rabbit model, infarct size was similarly reduced with a loading dose of 53.6 µg/kg followed by a 60 min infusion of 1.25 µg/kg/min (41.1 ± 3.1% infarction in control hearts to 16.0 ± 4.4% in treated hearts, P < 0.05). BAY-58 similarly decreased infarction in the isolated rat heart, and protection was abolished by co-treatment with a protein kinase G (PKG) antagonist, or a mitochondrial K_ATP channel antagonist. Conversely, N-nitro-L-arginine-methyl-ester-hydrochloride, a NO-synthase inhibitor, failed to block BAY-58's ability to decrease infarction, consistent with the latter's putative NO-independent activation of PKG. Finally, BAY-58 increased myocardial cGMP content in reperfused hearts while cAMP was unchanged.

When applied at reperfusion, BAY-58 is an effective cardioprotective agent with a mechanism similar to that of ischaemic pre-conditioning and, hence, should be a candidate for treatment of acute myocardial infarction in man.

Personal exposures to PM₁₀, PM_2.5, and PM_0.25 was measured over 24 h in 39 patients (36 males, 3 females; mean age 60.3 years) with prior myocardial infarction (>6 months). Simultaneously, a 24 h ECG was recorded and then analysed for HRV and ventricular arrhythmias. Breath condensate and blood samples also were collected at the end of monitoring to measure several indexes of inflammation. Negative correlation was found between HRV and exposure to PM_0.25 in a group of patients not taking β-blockers. More severe ventricular arrhythmias were observed at the highest concentrations of PM₁₀ and PM_2.5. Indexes of inflammation in either breath condensate or blood did not correlate with PM exposures.

Our study shows that exposure to ultrafine particles is associated with autonomic dysregulation in selected patients with myocardial infarction. More severe arrhythmias occur at the highest exposures to larger particles. Nevertheless, the underlying mechanisms remain hypothetical because inflammation may be evoked by PM or be related to the disease itself.

Since 1996, all patients with ischaemic heart disease, receiving ICD therapy for secondary prevention of sudden death, were included in the current study. Patients were evaluated at implantation and during long-term follow-up. A total of 456 patients were included in the analysis and followed for 54 ± 35 months. During follow-up, 100 (22%) patients died and ICD therapy was noted in 216 (47%) patients, of which 138 (30%) for fast, potentially life-threatening ventricular arrhythmia. Multivariate analysis revealed a history of atrial fibrillation or flutter (AF), ventricular tachycardia as presenting arrhythmia, and wide QRS and poor left ventricular ejection fraction as independent predictors of life-threatening ventricular arrhythmias. The strongest predictor was AF with a hazard ratio of 2.1 (95% confidence interval 1.3–3.2). On the basis of the available clinical data, it was not possible to identify a group which exhibited no risk on recurrence of potentially life-threatening ventricular arrhythmias.

Ischaemic secondary prevention ICD recipients exhibit a high recurrence rate of potentially life-threatening ventricular arrhythmias. Factors that increase risk can be identified but, even with these factors, it was not possible to distinguish a recurrence-free group.

Prevalence and depth of coronary artery bridges (CBs) were assessed in 255 hearts, including 115 with HCM (median age 29, range 5–90; 75% male), and 140 controls. Coronary artery bridges were more common in HCM (47/115; 41%) than in patients who died of a variety of non-HCM-related causes (21/100; 21%; P = 0.002), or in patients with congenital aortic stenosis and left ventricular (LV) hypertrophy (5/40; 12%; P = 0.001). Among the HCM hearts, CBs were present in 33 of 77 patients (43%) with sudden death, in 10 of 27 (37%) with heart failure death (or heart transplantation), and in 4 of 11 (36%) with other modes of death (P = 0.826). Deeply embedded CBs (≥2 mm) occurred with similar frequency in HCM patients with sudden (21 of 77; 27%) or heart failure death (5 of 27; 13%; P = 0.191). In sudden death patients, the presence of CB was unrelated to gender (33% in women and 45% in men, P = 0.406) and age (41% <18 years vs. 44% ≥18 years; P = 0.827).

In this morphological analysis of more than 250 hearts, CBs are a frequent component of phenotypically expressed HCM, and more common than in other disorders with or without LV hypertrophy. Although no systematic association with HCM-related sudden death is evident, our findings do not exclude the possibility that CB could contribute to increased risk in some individual patients, potentially impacting management decision-making on a case-by-case basis.

The study included 15 patients. Tako-tsubo cardiomyopathy was diagnosed by coronary angiography and ventriculography. Cardiac MRI was performed within 24 h of admission. Endomyocardial biopsies were taken during the acute phase and after recovery. The content of fibrosis was determined by immunohistochemical staining of collagen-1. In the acute phase, cardiac MRI revealed LGE in five patients. This was completely reversed at follow-up [14, inter-quartile range (IQR) 11–14.5 days]. All patients showed a significant increase of collagen-1 compared with control tissue. Moreover, the amount of collagen-1 was significantly higher in LGE positive patients (LGE positive: 18.84, IQR 13.82–19.75 AU/µm²; LGE negative: 7.57, IQR 5.41–9.19 AU/µm², P = 0.001). The presence of LGE was not associated with poorer left ventricular function.

The presence of LGE cannot rule out tako-tsubo cardiomyopathy. Instead it defines a special subgroup of patients with a disproportionate increase of extracellular matrix.

We measured left heart dimensions of 25 healthy twin pairs with a 1.5T MR scanner, analysed with the mass©, Medis Software. We performed heritability analysis and tests for genetic influences shared between cardiac structures. We found that CMR-based heritability estimates (h² = 84%) substantially exceeded estimates based on echocardiography. We also found significant genetic influence on papillary muscle mass (h² = 82%). Bivariate analysis of papillary and LV muscle mass revealed significant genetic influences shared by both phenotypes (genetic correlation 0.59) and suggested an additional genetic component specific to papillary muscle. We observed correlations between body mass index, surface area, and systolic blood pressure with cardiac dimensions, even in this small study. Environmental influences were relevant as well, indicating reciprocal influences on papillary vs. LV muscle mass.

Cardiovascular magnetic resonance, even with few subjects, allows a genetic assessment of cardiac structures that cannot be attained with echocardiography. Hitherto fore unappreciated relationships can be uncovered by this method.

We screened the promoter region of human calmodulin III gene (CALM3) and identified a new –34T>A polymorphism with a T-allele frequency of 0.70. The distribution of CALM3 genotypes differed in 180 unrelated FHC patients carrying a known FHC mutation compared with 134 controls, with higher TT-genotype frequency (0.73 vs. 0.51) and lower frequencies of AT- (0.24 vs. 0.37) and AA genotypes (0.03 vs. 0.11; P = 0.0005). To study whether the –34T>A polymorphism could play a modifier role, patients’ relatives including both affected and healthy carriers were added. Affected carriers had a 0.56 times higher odds of carrying a T allele than healthy carriers (P = 0.053). We then investigated whether the –34T>A polymorphism affects the promoter activity using luciferase reporter vectors containing either CALM3-T or CALM3-A promoters. The activity of CALM3-T was lower than CALM3-A in HEK293 cells (1.00 ± 0.19 vs. 2.31 ± 0.13, P = 0.00001) and in cardiomyocytes (0.96 ± 0.10 vs. 1.33 ± 0.08, P = 0.00727).

These data suggest that the –34T>A CALM3 polymorphism is a modifier gene for FHC, potentially by affecting expression level of CALM3 and therefore Ca²⁺-handling and development of hypertrophy.

PREAMI included 1252 post-AMI patients (age 73 ± 6 years, LV ejection fraction 59.1 ± 7.7%) receiving optimal therapy after AMI, randomized to perindopril 8 mg/day (n = 631) or placebo (n = 621); n = 896 had complete echo-Doppler data. Outcome measures were clinical [death, heart failure (HF)] and standard echo-Doppler parameters. Pre-discharge LV end-diastolic volume (LVEDV) was similar: 81.1 ± 23.1 (perindopril) and 79.6 ± 22.7 mL (placebo). At 6 months and 1 year, LVEDV remained unchanged with perindopril (81.2 ± 24.4 and 81.8 ± 26.8 mL, respectively), but increased with placebo (83.0 ± 25.3 and 83.6 ± 25.7 mL, respectively, both P < 0.001 vs. baseline). Perindopril reduced cardiac sphericity vs. placebo (P = 0.015 at 6 months; P = 0.020 at 1 year). Classification regression tree analysis showed treatment as the most important predictor of remodelling. Multiple pre-discharge echocardiographic variables predicted the death/HF endpoint, independently of treatment (P ≤ 0.05).

Remodelling occurs in post-AMI in elderly patients with normal LV function. Echo-Doppler variables at baseline have prognostic implications. Treatment with perindopril reduces progressive LV remodelling that can occur even in the case of small infarct size.

The EVEREST trial randomized 4133 patients hospitalized for worsening HF and low ejection fraction (≤40%) to tolvaptan, a vasopressin antagonist, or placebo. Following discharge, BW was assessed at 1, 4, and 8 weeks, and every 8 weeks thereafter. A time-dependent Cox proportional Hazard model explored the relationship between change in BW at 60, 120, and 180 days from discharge and the risks of HF hospitalization, cardiovascular (CV) hospitalization, and all-cause mortality. For subjects re-hospitalized for heart failure at 60, 120, and 180 days after discharge, mean BW increase prior to the event was 1.96, 2.07, and 1.97 kg, respectively, compared with 0.74, 0.90, and 1.04 kg in patients without re-hospitalization (P < 0.001 all groups). A similar pattern was observed with CV hospitalization. However, increases in BW were not predictive of all-cause mortality.

Increases in BW after hospitalization for worsening HF was predictive of repeat hospitalization events, but not mortality in the post-discharge period.