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.

Electrocardiographic evolution after Q-wave anterior myocardial infarction: correlations between QRS score and changes in left ventricular perfusion and function.

Background : By measuring the pressure decline caused by coronary narrowing, fractional
flow reserve (FFR) is an index of the physiological significance of a vessel stenosis. Intracoronary
electrocardiogram (IC-ECG) recording from an angioplasty guidewire is more sensitive
than standard ECG in detecting regional myocardial ischemia. The aim of the study was to
assess if unipolar IC-ECG ST segment recording from angioplasty guidewire during maximal
pharmacologic vasodilation could be used as an indirect estimation of FFR results.
 Methods : Forty-eight clinically stable patients with intermediate stenosis underwent FFR
evaluation and IC-ECG recording during intravenous adenosine infusion.
 Results : FFR values were ≤ 0.80 in 26 (54%) patients and > 0.80 in 22 (46%). After adenosine,
standard ECG was abnormal in only nine (19%) patients, while IC-ECG showed a significant
ST segment shift (IST) in 24 (50%) patients: ST elevation in 19 patients and depression
in five). IST was documented in 21/26 patients with FFR ≤ 0.80 (81%) and in 3/22 with FFR
> 0.80 (p Conclusions : Intracoronary ST segment shift evaluation during adenosine infusion may be
of value in assessing the functional significance of a borderline stenosis. The presence of
IST during adenosine infusion could obviate the need for additional FFR evaluation.
( Cardiol J 2011; 18, 6: 662–667 )

/pdf/intracoronary-electrocardiogram-st-segment-shift-evaluation-4j10hu7p7e.pdf

Michele Galli

Papers

Electrocardiographic evolution after Q-wave anterior myocardial infarction: correlations between QRS score and changes in left ventricular perfusion and function.

Intracoronary electrocardiogram ST segment shift evaluation during intravenous adenosine infusion: A comparison with fractional flow reserve

Silent ischemia during mental stress: scintigraphic evidence and electrocardiographic patterns.

Dipyridamole-induced negative U waves: scintigraphic evidence of severe anterior myocardial ischemia.

Risk stratification after myocardial infarction.