Prognostic impact of peripheral artery disease-related parameters in patients with acute coronary syndrome.

Background: Lower extremity arterial disease (LEAD) and increased aortic stiffness are associated with higher mortality in patients with chronic coronary syndrome, while their prognostic significance after an acute coronary syndrome (ACS) is less known.

Methods: We analyzed prevalence, clinical phenotypes and association of LEAD - assessed by the ankle-brachial index (ABI) - and increased aortic stiffness - assessed by the aortic pulse wave velocity (PWV) - with all-cause mortality and major adverse cardiovascular events (MACE) in patients admitted with an ACS.

Results: Among 270 patients admitted for ACS (mean age 67 years, 80% males), 41 (15%) had an ABI ≤0.

Mitochondrial DNA integrity and function are critical for endothelium-dependent vasodilation in rats with metabolic syndrome.

Endothelial dysfunction in diabetes is generally attributed to oxidative stress, but this view is challenged by observations showing antioxidants do not eliminate diabetic vasculopathy. As an alternative to oxidative stress-induced dysfunction, we interrogated if impaired mitochondrial function in endothelial cells is central to endothelial dysfunction in the metabolic syndrome. We observed reduced coronary arteriolar vasodilation to the endothelium-dependent dilator, acetylcholine (Ach), in Zucker Obese Fatty rats (ZOF, 34 ± 15% [mean ± standard deviation] 10 M) compared to Zucker Lean rats (ZLN, 98 ± 11%).

Myocardial ischemia: From disease to syndrome.

Although current guidelines on the management of stable coronary artery disease acknowledge that multiple mechanisms may precipitate myocardial ischemia, recommended diagnostic, prognostic and therapeutic algorithms are still focused on obstructive epicardial atherosclerotic lesions, and little progress has been made in identifying management strategies for non-atherosclerotic causes of myocardial ischemia. The purpose of this consensus paper is three-fold: 1) to marshal scientific evidence that obstructive atherosclerosis can co-exist with other mechanisms of ischemic heart disease (IHD); 2) to explore how the awareness of multiple precipitating mechanisms could impact on pre-test probability, provocative test results and treatment strategies; and 3) to stimulate a more comprehensive approach to chronic myocardial ischemic syndromes, consistent with the new understanding of this condition.

Trimetazidine and Other Metabolic Modifiers.

Treatment goals for people with chronic angina should focus on the relief of symptoms and improving mortality rates so the patient can feel better and live longer. The traditional haemodynamic approach to ischaemic heart disease was based on the assumption that increasing oxygen supply and decreasing oxygen demand would improve symptoms. However, data from clinical trials, show that about one third of people continue to have angina despite a successful percutaneous coronary intervention and medical therapy.

Echo-derived peak cardiac power output-to-left ventricular mass with cardiopulmonary exercise testing predicts outcome in patients with heart failure and depressed systolic function.

Aims: Peak cardiac power output-to-mass (CPOM) represents a measure of the rate at which cardiac work is delivered respect to the potential energy stored in left ventricular (LV) mass. We studied the value of CPOM and cardiopulmonary exercise test (CPET) in risk stratification of patients with heart failure (HF).

Materials And Results: We studied 159 patients with chronic HF (mean rest LV ejection fraction 30%) undergoing CPET and exercise stress echocardiography.

Prediction of Post Percutaneous Coronary Intervention Myocardial Ischaemia.

Following revascularisation the majority of patients obtain symptom relief and improved quality of life. However, myocardial ischaemia may recur or persist in a significant patient subset. Symptom recurrence is usually attributed to inaccurate evaluation of epicardial stenosis, incomplete revascularisation or stent failure and disease progression.

Pharmacological Agents Targeting Myocardial Metabolism for the Management of Chronic Stable Angina : an Update.

Despite continuous advances in myocardial revascularization procedures and intracoronary devices, patients with ischemic heart disease (IHD) still experience worse prognosis and poor quality of life (QoL). Indeed, chronic stable angina (CSA) is a common disease with a large burden on healthcare costs. Traditionally, CSA is interpreted as episodes of reversible myocardial ischemia related to the presence of stable coronary artery plaque causing myocardial demand/supply mismatch when myocardial oxygen consumption increases.

Impaired coronary metabolic dilation in the metabolic syndrome is linked to mitochondrial dysfunction and mitochondrial DNA damage.

Mitochondrial dysfunction in obesity and diabetes can be caused by excessive production of free radicals, which can damage mitochondrial DNA. Because mitochondrial DNA plays a key role in the production of ATP necessary for cardiac work, we hypothesized that mitochondrial dysfunction, induced by mitochondrial DNA damage, uncouples coronary blood flow from cardiac work. Myocardial blood flow (contrast echocardiography) was measured in Zucker lean (ZLN) and obese fatty (ZOF) rats during increased cardiac metabolism (product of heart rate and arterial pressure, i.

Stress Testing After Complete and Successful Coronary Revascularization.

Background: Noninvasive stress tests play a determinant role in the initial management of patients with chronic angina. Nonetheless, their use in the same patient population is considered inappropriate within 2 years after percutaneous coronary intervention (PCI). Indeed, early abnormal results correlate less well with angiographic control and are attributed to a number of confounding factors.

Pharmacological approaches to coronary microvascular dysfunction.

In recent decades coronary microvascular dysfunction has been increasingly identified as a relevant contributor to several cardiovascular conditions. Indeed, coronary microvascular abnormalities have been recognized in patients suffering acute myocardial infarction, chronic stable angina and cardiomyopathies, and also in patients with hypertension, obesity and diabetes. In this review, we will examine pathophysiological information needed to understand pharmacological approaches to coronary microvascular dysfunction in these different clinical contexts.

BCNU-induced gR2 defect mediates S-glutathionylation of Complex I and respiratory uncoupling in myocardium.

A deficiency of mitochondrial glutathione reductase (or GR2) is capable of adversely affecting the reduction of GSSG and increasing mitochondrial oxidative stress. BCNU [1,3-bis (2-chloroethyl)-1-nitrosourea] is an anticancer agent and known inhibitor of cytosolic GR ex vivo and in vivo. Here we tested the hypothesis that a BCNU-induced GR2 defect contributes to mitochondrial dysfunction and subsequent impairment of heart function.

Defining the role of high-dose statins in PCI.

Several studies have reported a significant reduction in morbidity and mortality in patients with acute coronary syndrome (ACS) or in patients with stable ischemic heart disease with the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Based on these findings, current guidelines recommend the use of statin therapy before hospital discharge for all patients with ACS regardless of the baseline low-density lipoprotein level. Statins are also recommended to patients at high risk for cardiovascular disease.

Ultrasound assessment of the force-frequency relationship from the law of conservation of momentum in patients with left ventricular dysfunction.

Measurement of force-frequency relationship (FFR) is useful in the evaluation of heart rate-dependent contractile dysfunction. The purpose of this study was to evaluate a new Doppler-derived method for assessing FFR. Doppler velocity spectra at the left ventricular (LV) outflow tract was used to estimate mean blood flow velocity (mBFV), ejection time (ET) and velocity-time integral.

Therapy against ischemic injury.

The advent of reperfusion therapy constituted a historical change for the management of myocardial infarction (MI) patients. However, shortly after, experimental models recognized an intrinsic damage, related to reperfusion itself, which was termed as ischemiareperfusion injury (IRI). Clinical studies attribute IRI a significant burden of morbidity and mortality observed in patients undergoing successful epicardial reperfusion.

Microvascular function/dysfunction downstream a coronary stenosis.

For decades coronary macrovascular atherosclerosis has been considered the principal manifestation of coronary heart disease, with most of our effort dedicated to identifying and removal of coronary stenosis. However, growing body of literature indicates that coronary microcirculation also contributes substantially to the pathophysiology of cardiovascular disease. An understanding of mechanisms regulating microvascular function is of critical importance in understanding its role in disease, especially because these regulatory mechanisms vary substantially across species, vascular bed and due to comorbidities.

The second law of thermodynamics and the heart.

The second law of thermodynamics explains the phenomenon of irreversibility and the increasing entropic trend of nature. Similar to human-made machines, living structures are subjected to entropy generation, becoming 'worn' and 'damaged' from use. However, they have the possibility of eluding or deferring these processes.

Obstructive coronary atherosclerosis and ischemic heart disease: an elusive link!

In the current pathophysiological model of chronic ischemic heart disease (IHD), myocardial ischemia and exertional angina are caused by obstructive atherosclerotic plaque, and the clinical management of IHD is centered on the identification and removal of the stenosis. Although this approach has been in place for years, several lines of evidence, including poor prognostic impact, suggest that this direct relationship may present an oversimplified view of IHD. Indeed, a large number of studies have found that IHD can occur in the presence or absence of obstructive coronary artery disease and that atherosclerosis is just 1 element in a complex multifactorial pathophysiological process that includes inflammation, microvascular coronary dysfunction, endothelial dysfunction, thrombosis, and angiogenesis.

Disruption of TRPV1-mediated coupling of coronary blood flow to cardiac metabolism in diabetic mice: role of nitric oxide and BK channels.

We have previously shown transient receptor potential vanilloid subtype 1 (TRPV1) channel-dependent coronary function is compromised in pigs with metabolic syndrome (MetS). However, the mechanisms through which TRPV1 channels couple coronary blood flow to metabolism are not fully understood. We employed mice lacking TRPV1 [TRPV1((-/-))], db/db diabetic, and control C57BKS/J mice to determine the extent to which TRPV1 channels modulate coronary function and contribute to vascular dysfunction in diabetic cardiomyopathy.

Right ventricular dysfunction is associated with chronic kidney disease and predicts survival in patients with chronic systolic heart failure.

Aims: Chronic kidney disease (CKD) and right ventricular (RV) dysfunction are important predictors of prognosis in heart failure (HF). We investigated the relationship between RV dysfunction and CKD in outpatients with chronic systolic HF, an association which remains poorly defined.

Methods And Results: Outpatients (n = 373) with chronic HF and left ventricular ejection fraction (LVEF) ≤45% underwent clinical and echo-Doppler evaluations and were followed up for 31 ± 24 months.