Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.

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Finding the missing heritability of complex diseases

Recommendations for the evaluation of left ventricular diastolic function by echocardiography

Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography : An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging

http://www.jse.gr.jp/2016_LVDiastolicFunction.pdf

Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging

The assessment of left ventricular (LV) diastolic function should be an integral part of a routine examination, particularly in patients presenting with dyspnea or heart failure. About half of patients with new diagnoses of heart failure have normal or near normal global ejection fractions (EFs). These patients are diagnosed with “diastolic heart failure” or “heart failure with preserved EF.”1 The assessment of LV diastolic function and filling pressures is of paramount clinical importance to distinguish this syndrome from other diseases such as pulmonary disease resulting in dyspnea, to assess prognosis, and to identify underlying cardiac disease and its best treatment.

LV filling pressures as measured invasively include mean pulmonary wedge pressure or mean left atrial (LA) pressure (both in the absence of mitral stenosis), LV end-diastolic pressure (LVEDP; the pressure at the onset of the QRS complex or after A-wave pressure), and pre-A LV diastolic pressure (Figure 1).Although these pressures are different in absolute terms, they are closely related, and they change in a predictable progression with myocardial disease, such that LVEDP increases prior to the rise in mean LA pressure.



Figure 1 
The 4 phases of diastole are marked in relation to high-fidelity pressure recordings from the left atrium (LA) and left ventricle (LV) in anesthetized dogs. The first pressure crossover corresponds to the end of isovolumic relaxation and mitral valve opening. In the first phase, left atrial pressure exceeds left ventricular pressure, accelerating mitral flow. Peak mitral E roughly corresponds to the second crossover. Thereafter, left ventricular pressure exceeds left atrial pressure, decelerating mitral flow. These two phases correspond to rapid filling. This is followed by slow filling, with almost no pressure differences. During atrial contraction, left atrial pressure again exceeds left ventricular pressure. The solid arrow points to left ventricular minimal pressure, the dotted arrow to left ventricular …

https://biblio.ugent.be/publication/631868/file/631869.pdf

Background Recent studies indicate that magnetic resonance imaging (MRI) after the administration of contrast material can be used to distinguish between reversible and irreversible myocardial ischemic injury regardless of the extent of wall motion or the age of the infarct. We hypothesized that the results of contrast-enhanced MRI can be used to predict whether regions of abnormal ventricular contraction will improve after revascularization in patients with coronary artery disease. Methods Gadolinium-enhanced MRI was performed in 50 patients with ventricular dysfunction before they underwent surgical or percutaneous revascularization. The transmural extent of hyperenhanced regions was postulated to represent the transmural extent of nonviable myocardium. The extent of regional contractility at the same locations was determined by cine MRI before and after revascularization in 41 patients. Results Contrast-enhanced MRI showed hyperenhancement of myocardial tissue in 40 of 50 patients before revascularizat...

https://www.nejm.org/doi/pdf/10.1056/NEJM200011163432003

The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction.

Background— Elevation of cardiac biomarkers after coronary angioplasty (percutaneous coronary intervention [PCI]) reflects periprocedural myocardial damage and is associated with adverse cardiac events. We assessed whether periprocedural myocardial damage that occurs despite successful PCI could be rapidly and easily identified by intracoronary ST-segment recording with the use of a catheter guidewire. Methods and Results— In 108 consecutive stable patients undergoing elective single-vessel PCI, we recorded unipolar ECG from the intracoronary guidewire in the distal coronary before PCI and 2 minutes after the last balloon inflation. After PCI, intracoronary ST-segment shift ≥1 mm from baseline was considered significant. Troponin I levels were measured at baseline and at 8 and 24 hours after intervention, and myocardial damage was defined as troponin I increase above the upper normal value after intervention. All patients had normal cardiac marker values before PCI, and PCI was successful in all (residual...

Intracoronary ST-segment shift soon after elective percutaneous coronary intervention accurately predicts periprocedural myocardial injury.

UNLABELLED Lung uptake of 201Tl is a reliable marker of left ventricular dysfunction. The goal of our study was to establish whether the evaluation of lung-to-heart uptake ratios (LHR) with 99mTc-sestamibi imaging may provide valuable information. METHODS We studied 72 male subjects with recent anterior myocardial infarction undergoing 99mTc-sestamibi first-pass ventriculography and SPECT perfusion imaging. A group of 46 gender-matched subjects with low pre-test likelihood of CAD and normal exercise and rest 99mTc-sestamibi perfusion images was used as a control. The lung-to-heart count ratios (LHR) were calculated on planar projections from the sets of SPECT images. RESULTS Both groups were studied at rest and after a symptom-limited exercise tolerance test. In the control group a significant decrease in LHR was observed during stress (p < 0.001). The infarcted group showed significantly higher LHR values both at rest and at stress. Exercise and rest LHR values did not differ significantly. A positive correlation was observed between LHR values and left ventricular ejection fraction at rest and stress. CONCLUSION LHR, measured by 99mTc-sestamibi imaging, gives clinically useful information. Both resting and postexercise values are correlated with ejection fraction and should predict left ventricular dysfunction.

http://jnm.snmjournals.org/content/36/1/58.full.pdf

Evaluation of technetium-99m-sestamibi lung uptake: correlation with left ventricular function.

Tissue plasminogen activator antigen is strongly associated with myocardial infarction in young women

A relative paucity of information concerns the natural history, clinical features and coronary anatomy in young patients with acute myocardial infarction. In particular, there is a dearth of data relating to sex differences in young patients. The objective was to evaluate whether or not there are correlations between the clinical characteristics and the extent and localization of coronary artery lesions in young men compared with young women. The study population consisted of 1646 young patients (87% men, 13% women; mean age 39+/-5 years) with a first acute myocardial infarction admitted to one of the 125 coronary care units of Italy in a period of 3 years. Clinical data were collected. All patients underwent coronary angiography during hospitalization. Smoking, hypercholesterolemia and obesity were significantly more prevalent in men than in women; physical inactivity was significantly more prevalent among women. Hemodynamically significant coronary stenosis occurred in 82% of patients and were more frequent in men than in women (P<0.05). Women more frequently had single-vessel disease and no coronary lesions at all (58 vs. 47% and 24 vs. 9% women vs. men respectively, both P<0.05). Men more frequently had multivessel disease (38 vs. 13%, P<0.05). Significant stenosis mainly affected the left anterior descending artery (52%) with no gender-related difference; men more likely had lesions of the left circumflex or right coronary artery (P<0.05). In conclusion, young patients with a first acute myocardial infarction risk factors profile and extent of coronary artery lesions were significantly different between sexes.

Myocardial infarction in the young: a sex-based comparison.

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Michele Galli

Papers

Intracoronary ST-segment shift soon after elective percutaneous coronary intervention accurately predicts periprocedural myocardial injury.

Evaluation of technetium-99m-sestamibi lung uptake: correlation with left ventricular function.

Tissue plasminogen activator antigen is strongly associated with myocardial infarction in young women

Myocardial infarction in the young: a sex-based comparison.

Dobutamine stress echocardiography.