Glucose tolerance and markers of myocardial injury after an acute coronary syndrome: predictive role of the 1-h plus 2-h plasma glucose at the oral glucose tolerance test.

OBJECTIVE: Impaired glucose tolerance (IGT) has been related to adverse cardiovascular outcomes. We investigated the added value of 1-h plasma glucose (PG) at the oral glucose tolerance test (OGTT) in predicting admission and peak cardiac high-sensitivity troponin T (hs-TnT) and NT-proBNP values in IGT patients admitted for an acute coronary syndrome (ACS). RESEARCH DESIGN AND METHODS: Among 192 consecutive ACS patients, 109 had Hb1Ac and fasting plasma glucose negative for newly diagnosed diabetes. Upon OGTT performed > 96 h after admission, 88, conventionally diagnosed as IGT, were divided into: "full glucose tolerance" (1-h PG-OGTT < 155 mg/dL and 2-h PG-OGTT < 140 mg/dL, N = 12);"early IGT" (1 h-PG-OGTT ≥ 155 mg/dL and 2-h PG-OGTT < 140 mg/dL, N = 33);"late IGT" (1-h PG-OGTT < 155 mg/dL and 2-h PG-OGTT ≥ 140 mg/dL, N = 8); and "full IGT" (1-h PG-OGTT ≥ 155 mg/dL and 2-h PG-OGTT ≥ 140 mg/dL, N = 35). The 4 groups were compared for cardiac markers. RESULTS: The first three groups had similar cardiac marker values, but only full IGT patients had significantly higher admission hs-TnT compared with the 3 other groups [median (interquartile range): 911 (245-2976) vs 292 (46-1131), P < 0.001]. Full IGT patients also had higher hs-TnT peak compared with fully glucose tolerant and early IGT patients. Only full IGT patients had longer hospitalization and higher NT-proBNP vs fully glucose tolerant patients (P = 0.005). CONCLUSIONS: Among non-diabetic ACS patients, only those with both 1-h PG ≥ 155 mg/dL and 2-h PG ≥ 140 mg/dL had more severe myocardial injury and longer hospitalization. One-h PG-OGTT importantly contributes to assessing post-ACS cardiac risk.

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. Moreover, several trials on chronic stable angina therapy and revascularisation have failed to show benefits in terms of primary outcome (survival, cardiovascular death, all-cause mortality), symptom relief or echocardiographic parameters. Failure to significantly improve quality of life and prognosis may be attributed in part to a limited understanding of ischaemic heart disease, by neglecting the fact that ischaemia is a metabolic disorder. Shifting cardiac metabolism from free fatty acids towards glucose is a promising approach for the treatment of patients with stable angina, independent of the underlying disease (macrovascular and/or microvascular disease). Cardiac metabolic modulators open the way to a greater understanding of ischaemic heart disease and its common clinical manifestations as an energetic disorder rather than an imbalance between the demand and supply of oxygen and metabolites.

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. We prospectively assessed prevalence and impact on the quality of life of abnormal stress test results in a highly selected patient population. METHODS: Patients with no cardiac comorbidities who underwent successful and complete PCI with stenting for typical angina and had an abnormal exercise stress test (EST) under guideline-directed medical treatment were administered the Seattle Angina Questionnaire (SAQ). Clinical evaluation, EST, and the SAQ were repeated at 1, 6, and 12 months after the index PCI. RESULTS: One hundred ninety-eight patients qualified and were included in the study (mean age, 64 years; 79% men). Although the majority had normal EST results or an increased threshold to angina, at 1 month after the index PCI, 29% of patients still had an abnormal result. At 6 and 12 months, 31% and 29% of patients had abnormal results, respectively. Quality-of-life assessment by the SAQ showed consistent results, with persistent angina in one third of patients. Control angiography documented a critical lesion, attributable to in-stent coronary restenosis, in only 8% of patients. CONCLUSIONS: When stress testing is systematically performed after PCI, the prevalence of abnormal results is high and is associated with impaired quality of life. Prognostic significance along with the underlying pathophysiological mechanisms of such findings should be investigated.

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. Well-established drugs and new pharmacological agents, including those for which only preclinical data are available, will be covered in detail.

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. Several mechanisms have been identified and, as many strategies, have been investigated to address the phenomenon. In this review we will discuss the current evidence for IRI, pharmacological and non-pharmacological preventive strategies adopted both in experimental models and in clinical practice. Finally, we will try to provide a critical appraisal to the lack of consistent benefit observed in translational medicine.

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. Indeed, the most obvious consequence of coronary stenosis is that it may limit blood supply to the dependent myocardium to the point of causing ischaemia during exercise or even at rest. However, this flow limiting effect is not only due to the passive hydraulic effect of a narrowed conduit, but also to active responses in the coronary microcirculation triggered by the presence of an epicardial stenosis. To understand this problem it is important to review the inter-related mechanisms that regulate flow to the left ventricular wall and modulate transmural distribution of flow. These regulatory mechanisms operate hierarchically and are heterogeneously distributed along the coronary vascular tree. It is also important to discuss the effect of myocardial performance in modulating both blood flow demands and coronary resistance. Some of the interactions between coronary stenosis and microcirculation are transient, like those documented in acute coronary syndromes or during percutaneous interventions. However, microcirculatory remodeling may be triggered by a chronic coronary stenosis, leading to a sustained impairment of blood supply even after successful removal of the epicardial stenosis. A deeper understanding of these phenomena may explain paradoxical findings in patients undergoing coronary revascularization, particularly when functional tests are used in their assessment. These aspects are discussed in detail in this review.

The left ventricle as a mechanical engine: from Leonardo da Vinci to the echocardiographic assessment of peak power output-to-left ventricular mass.

The interpretation of the heart as a mechanical engine dates back to the teachings of Leonardo da Vinci, who was the first to apply the laws of mechanics to the function of the heart. Similar to any mechanical engine, whose performance is proportional to the power generated with respect to weight, the left ventricle can be viewed as a power generator whose performance can be related to left ventricular mass. Stress echocardiography may provide valuable information on the relationship between cardiac performance and recruited left ventricular mass that may be used in distinguishing between adaptive and maladaptive left ventricular remodeling. Peak power output-to-mass, obtained during exercise or pharmacological stress echocardiography, is a measure that reflects the number of watts that are developed by 100 g of left ventricular mass under maximal stimulation. Power output-to-mass may be calculated as left ventricular power output per 100 g of left ventricular mass: 100× left ventricular power output divided by left ventricular mass (W/100 g). A simplified formula to calculate power output-to-mass is as follows: 0.222 × cardiac output (l/min) × mean blood pressure (mmHg)/left ventricular mass (g). When the integrity of myocardial structure is compromised, a mismatch becomes apparent between maximal cardiac power output and left ventricular mass; when this occurs, a reduction of the peak power output-to-mass index is observed.

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. Furthermore, the high recurrence rates underscore the fact that removing stenosis in patients with stable IHD does not address the underlying pathological mechanisms that lead to the progression of nonculprit lesions. The model proposed herein shifts the focus away from obstructive epicardial coronary atherosclerosis and centers it on the microvasculature and myocardial cell where the ischemia is taking place. If the myocardial cell is placed at the center of the model, all the potential pathological inputs can be considered, and strategies that protect the cardiomyocytes from ischemic damage, regardless of the causative mechanism, can be developed.

Right ventricular remodelling in systemic hypertension: a cardiac MRI study.

BACKGROUND: Consistent evidence shows an impact of systemic haemodynamic overload on the right ventricle, but its functional and structural consequences have received scarce attention for several reasons including the difficult application of conventional imaging techniques due to the complex shape and orientation of that cardiac chamber. AIMS: To evaluate whether mild to moderate, uncomplicated hypertension associates with abnormal right ventricular structure and function and how those changes relate to homologous changes in the left ventricle. Data were acquired by steady-state free-precession cardiac MRI, the state of the art tool for the morphological and functional evaluation of the right ventricle. MATERIALS AND METHODS: Twenty-five (12 women) uncomplicated, untreated, essential hypertensive patients were compared with 24 (13 women) sedentary normotensive controls of comparable age. Wall thickness, indexed ventricular mass, end-diastolic volumes, early peak filling rate, a correlate of diastolic relaxation, and ejection fraction were measured at both ventricles. Remodelling index, the ratio of ventricular mass to end-diastolic volume, was used as an index of concentricity. RESULTS: Right ventricular mass index, ventricular wall thickness and remodelling index were greater in hypertensive subjects and associated with reduced peak filling rate, a pattern consistent with concentric right ventricular remodelling. In the hypertensive group, positive, highly significant biventricular correlations existed between indexed mass, early peak filling rate and ejection fraction. CONCLUSIONS: Systemic hypertension associates with concentric right ventricular remodelling and impaired diastolic function, confirming that the unstressed ventricle is not immune to the effects of systemic hypertension. Structural and functional right ventricular adaptation to systemic hypertension tends to parallel the homologous modifications induced by systemic haemodynamic overload on the left ventricle.

Patterns of left ventricular remodeling in chronic heart failure: prevalence and prognostic implications.

BACKGROUND AND AIM: Many descriptors of left ventricular (LV) remodeling have important prognostic implications in patients with chronic systolic heart failure (HF). We sought to assess the prognostic value of the combination of increased LV mass with a disproportion between wall thickness and internal diameter. METHODS AND PATIENTS: Patients (n = 536) with chronic HF, ejection fraction <50% and LV end-diastolic volume index >91 mL/m(2), classified according to LV mass index and relative wall thickness (RWT), were followed up for 33 ± 21 months. Ventricular mass was determined using a standard M-mode echocardiographic method. Relative wall thickness was defined as the ratio of (sum of interventricular septum thickness in diastole + posterior wall thickness in diastole)/LV end-diastolic diameter. RESULTS: Prevalence of the pattern of increased LV mass index, defined as LV mass index >148 g/m(2) in men and >122 g/m(2) in women, and decreased RWT (<0.34) was 29%. Multivariable predictors of all-cause mortality were age >70 years (P < .0001), New York Heart Association class >2 (P < .0001), increased LV mass index, and decreased RWT (P = .003), E wave deceleration time ≤140 ms (P = .005), and male gender (P = .025). Patients with increased LV mass index and decreased RWT had a worse survival (33%) than patients with less LV mass index and normal to reduced RWT (log-rank 23.92; P < .0001). Comparisons of Cox models showed that the combination of increased mass index and decreased RWT added prognostic value to a model that included ejection fraction and end-systolic volume index. CONCLUSION: In patients with systolic HF, an independent and incremental risk of adverse outcome was associated with increased mass index and decreased RWT.

Recurrent episodes of very late stent thrombosis in a patient with aspirin hypersensitivity, stent fracture and malapposition.

Late stent thrombosis represents a life-threatening event, usually triggered by inadequate antiplatelet therapy and promoted by multiple risk factors, such as stenting of a chronic total occlusion, overlapping stenting, an abnormal vascular response to the eluted drug, stent malapposition and stent fracture. A 57-year-old man with aspirin hypersensitivity underwent successful percutaneous revascularization of a chronic total occlusion of the left anterior descending artery (LAD). He received two sirolimus-eluting stents overlapping for 2 mm and was discharged on clopidogrel and picotamide. Two years later, 15 days after clopidogrel discontinuation, he experienced an anterior ST-segment elevation myocardial infarction and underwent rescue percutaneous LAD thrombectomy after unsuccessful fibrinolysis. Coronary angiography showed fracture of the distal stent, with a 5 mm gap between the two portions, as well as severe late stent malapposition, confirmed by optical coherence tomography. Despite treatment with clopidogrel and picotamide, in the following days the patient experienced two new episodes of stent thrombosis, treated with thrombectomy and deployment of bioengineered stents. The patient underwent successful oral aspirin desensitization, with a complete in vitro inhibition of platelet function, and was discharged on aspirin, clopidogrel and warfarin, without experiencing other events at 6-month follow-up.