Investigation of Associated Diseases in Acute Myocardial Infarction and Heart Failure: Metabolomic Insights

A 52-year-old obese male without a prior history of diabetes mellitus (DM) presented with angina and an anterior ST-segment–elevation myocardial infarction (STEMI). Physical examination and chest x-ray were consistent with congestive heart failure. Admission glucose was 230 mg/dL. Coronary angiography revealed an occluded left anterior descending coronary artery, and stenting reestablished TIMI grade 2 flow in that artery within 90 minutes of symptom onset. Left ventricular ejection fraction was 35% with severe anterior hypokinesis. Peak creatine kinase was 600 IU. The next day, fasting glucose was 180 mg/dL. An echocardiogram performed 6 weeks after discharge revealed an ejection fraction of 35% without change in the anterior wall motion. Fasting glucose as an outpatient was 156 mg/dL. The scenario described above is commonly encountered and illustrates how hyperglycemia can affect the outcome of patients with STEMI. Hyperglycemia could have affected the following features of this case: (1) Congestive heart failure was present despite only modest myocardial injury by creatine kinase level; (2) despite successful percutaneous coronary intervention, subnormal coronary perfusion was observed; and (3) left ventricular recovery after STEMI did not occur. Cardiologists need to be cognizant of the hazards associated with hyperglycemia in this setting because these patients will be encountered more frequently as a result of the increasing prevalence of insulin resistance syndromes. Acute hyperglycemia is common in patients with STEMI even in the absence of a history of type 2 DM. Hyperglycemia is encountered in up to 50% of all STEMI patients, whereas previously diagnosed DM is present in only 20% to 25% of STEMI patients.1 The prevalence of type 2 DM or impaired glucose tolerance may be as high as 65% in MI patients without prior DM when oral glucose tolerance testing is performed.2 Elevated …

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

Nitrates are potent venous dilators and anti-ischemic agents. They are widely used for the relief of chest pain and pulmonary congestion in patients with acute coronary syndromes and heart failure. Nitrates, however, do not reduce mortality in patients with acute coronary syndromes. Combination of nitrates and hydralazine when given in addition to β-blockers and angiotensin-converting enzyme (ACE) inhibitors reduce mortality and heart failure hospitalizations in patients with heart failure due to left ventricular systolic dysfunction who are of African–American origin. Side effects during nitrate therapy are common but are less well described in the literature compared with the reported side effects in patients with stable angina pectoris. The reported incidence of side effects varies highly among different studies and among various disease states. Headache is the most commonly reported side effect with an incidence of 12% in acute heart failure, 41 – 73% in chronic heart failure, 3 – 19% in unstable angina and 2 – 26% in acute myocardial infarction. The reported incidence of hypotension also differs: 5 – 10% in acute heart failure, 20% in chronic heart failure, 9% in unstable angina and < 1 – 48% in acute myocardial infarction, with the incidence being much higher with concomitant nitrate therapy plus angiotensin-converting enzyme inhibitors. Reported incidence of dizziness is as low as 1% in patients with acute myocardial infarction to as high as 29% in patients with heart failure. Severe headaches and/or symptomatic hypotension may necessitate discontinuation of nitrate therapy. Severe life threatening hypotension or even death may occur when nitrates are used in patients with acute inferior myocardial infarction associated with right ventricular dysfunction or infarction, or with concomitant use of phosphodiesterase-5 inhibitors or N-acetylcysteine. Despite the disturbing observational reports in the literature that continuous and prolonged use of nitrates may lead to increased mortality and recurrent myocardial infarction in patients with stable coronary artery disease, no such adverse effects of nitrates have been reported in the large randomized trials in patients with acute myocardial infarction or chronic heart failure.

Cardiovascular News

In the early development of therapy for acute myocardial infarction, it was thought that once the necrotic process had been completed (usually within 24 hours of coronary artery occlusion), additional therapies could not affect outcome. However, after completion of the necrotic process, the myocardial infarction may thin and stretch (involving lengthwise slippage of myocytes), a phenomenon referred to as myocardial infarct expansion. This process causes local left ventricular cavity dilatation followed by gradual global left ventricular dilatation and lengthwise (eccentric) hypertrophy of the noninfarcted tissue. Apoptosis (programmed cell death) and some attempt of the myocardium to regenerate, especially at the infarct border zone, may also contribute to this remodeling process of the ventricle. If the left ventricle remodels in such a way that it becomes very dilated, then the prognosis is poor, and heart failure is more likely to occur.1 These later processes of myocardial infarct expansion and left ventricular remodeling became the target of therapies such as angiotensin-converting enzyme (ACE) inhibition that could be initiated after 24 hours of coronary occlusion. ACE inhibition, angiotensin receptor blockade, and long-term β-blockade have become standard pharmacological approaches for postinfarction left ventricular dysfunction and heart failure. Response by Pitt and Pitt p 2989 Ventricular arrhythmias can occur in both the acute and chronic phases of acute myocardial infarction and can lead to sudden cardiac death (SCD). Reentrant arrhythmias may arise at the border zone of infarcts, causing monomorphic ventricular tachycardia that may occur years after the index infarction. Recurrent myocardial ischemia resulting in an unstable substrate may contribute to polymorphic ventricular tachycardia or ventricular fibrillation. Agents such as β-blockers that are anti-ischemic may reduce sudden death by quieting this unstable substrate. In the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II, implantable defibrillators were shown to reduce mortality in post–myocardial infarction patients with …

Preamble......237 Medicine is experiencing an unprecedented focus on quantifying and improving health care quality. The American College of Cardiology (ACC) and the American Heart Association (AHA) have developed a multi-faceted strategy to facilitate the process of improving clinical care. The

In patients admitted for acute stroke, the clinical burden of acute myocardial infarction (AMI) and acute heart failure (AHF) is unclear. In these patients we evaluated: (1) the prevalence of AMI and AHF; (2) the effect of AMI and/or AHF on mortality at 3 months; (3) the risk factors for AMI and/or AHF. Consecutive patients admitted for acute stroke were prospectively assessed for the occurrence of AMI and AHF during the hospital stay. Mortality at 3 months was also assessed. Multiple logistic regression analysis was used to identify independent predictors for cardiovascular events and death. Eight hundred fourteen patients were included in the study, 685 of which had an ischemic stroke (84.2%). Fifty-three patients (6.5%) had an AMI and/or an AHF (13 AMI alone, 28 AHF alone and 12 AMI and AHF); all these events occurred in patients with ischemic stroke. At 3 months, 151 patients had died (18.8%). Among patients who had an AMI and/or AHF, 60.4% died as compared with 119 of the 750 patients who did not have these events (15.9%) (p < 0.0001). At logistic regression analysis, AMI and/or AHF were associated with increased mortality at 3 months (p = 0.001). History of angina (p = 0.003), AMI in the 3 months before admission (p < 0.0001), hyperglycemia (p = 0.047), and high NIHSS on admission (p < 0.0001) were associated with in hospital AMI and/or AHF. In acute stroke patients, AMI and AHF are common and associated with increased mortality at 3 months. Whether a timely and more careful management of these complications may improve clinical outcome should be further explored.

Inferior myocardial infarction (MI) is considered to have a more favorable prognosis than anterior wall MI but includes high risk groups with increased mortality and morbidity. It is well known that congestive heart failure (CHF) complicating acute MI has poor prognosis. In this study we assessed the clinical and prognostic significance of CHF and the predictive value of the baseline demographic and clinical variables for CHF in patients with acute inferior MI. A total of 350 patients with acute inferior MI were included. In group A there were 26 patients (7.4%) with CHF, and in group B there were 324 patients (92.6%) without this complication. Baseline clinical and demographic characteristics and in-hospital complications of the groups were assessed. In group A patients were older (67.6 ± 9.5 vs 53.7 ± 10.9 years, p < 0.0001) and there were more female patients (50% vs 15%, p < 0.00001) compared to group B. The prevalence of diabetes mellitus (58% vs 16%) and precordial ST segment depression on admission ECG (81% vs 50%) were significantly higher in group A compared to group B (p < 0.00001 and p=0.002 consecutively). In group A there was a higher rate of righ ventricular (25% vs 23%), posterior (26% vs 24%) and posterolateral myocardial infarction (19% vs 14%), but the differences were not statistically different. In group A patients had significantly higher rate of second- or third-degree AV block (46% vs 8%, p < 0.00001), cardiogenic shock (35% vs 1%, p < 0.00001) and mortality (46% vs 3%, p < 0.00001) compared to group B. In a multivariate regression analysis diabetes mellitus (p=0.0003) and precordial ST segment depression on admission ECG (p=0.002) were found as the independent predictors of in-hospital CHF in patients with acute inferior MI. CHF and ST segment depression on admission ECG were found as the independent predictors of in-hospital mortality (p < 0.00001, p=0.04 consecutively). Patients with CHF complicating acute inferior MI have more unfavorable demographic and clinical characteristics on admission, higher rate of in-hospital complications and mortality. History of diabetes mellitus and precordial ST segment depression on admission ECG have an independent predictive value for CHF in this particular group of patients.

Management of Acute Coronary Syndromes

Inferior myocardial infarction (MI) is considered to have a more favorable prognosis than anterior wall MI but includes high risk groups with increased mortality and morbidity. It is well known that congestive heart failure (CHF) complicating acute MI has poor prognosis. In this study we assessed the clinical and prognostic significance of CHF and the predictive value of the baseline demographic and clinical variables for CHF in patients with acute inferior MI. A total of 350 patients with acute inferior MI were included. In group A there were 26 patients (7.4%) with CHF, and in group B there were 324 patients (92.6%) without this complication. Baseline clinical and demographic characteristics and in-hospital complications of the groups were assessed. In group A patients were older (67.6 ± 9.5 vs 53.7 ± 10.9 years, p < 0.0001) and there were more female patients (50% vs 15%, p < 0.00001) compared to group B. The prevalence of diabetes mellitus (58% vs 16%) and precordial ST segment depression on admission ECG (81% vs 50%) were significantly higher in group A compared to group B (p < 0.00001 and p=0.002 consecutively). In group A there was a higher rate of righ ventricular (25% vs 23%), posterior (26% vs 24%) and posterolateral myocardial infarction (19% vs 14%), but the differences were not statistically different. In group A patients had significantly higher rate of second- or third-degree AV block (46% vs 8%, p < 0.00001), cardiogenic shock (35% vs 1%, p < 0.00001) and mortality (46% vs 3%, p < 0.00001) compared to group B. In a multivariate regression analysis diabetes mellitus (p=0.0003) and precordial ST segment depression on admission ECG (p=0.002) were found as the independent predictors of in-hospital CHF in patients with acute inferior MI. CHF and ST segment depression on admission ECG were found as the independent predictors of in-hospital mortality (p < 0.00001, p=0.04 consecutively). Patients with CHF complicating acute inferior MI have more unfavorable demographic and clinical characteristics on admission, higher rate of in-hospital complications and mortality. History of diabetes mellitus and precordial ST segment depression on admission ECG have an independent predictive value for CHF in this particular group of patients.

Since the initial description of angiotensin II–mediated hypertension >40 years ago, basic and clinical investigations of the renin-angiotensin system (RAS) have resulted in a broader understanding of cardiovascular pathophysiology and significant advances in therapy. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists are now widely prescribed for the treatment of hypertension and left ventricular (LV) dysfunction; more recently, the aldosterone receptor antagonist, spironolactone, has proven beneficial in severe heart failure. This article will focus on our current understanding of the RAS and how pharmacological manipulation of this system can improve clinical outcomes in patients with cardiovascular disease. ### Pathophysiological Rationale for RAS Manipulation Renin is released by juxtuloglomerular cells in the kidney in response to renal hypoperfusion, decreased sodium delivery, and sympathetic activation (Figure 1). Angiotensinogen produced by the liver is cleaved by renin to yield the inactive decapeptide angiotensin I. Circulating angiotensin I is, in turn, converted to angiotensin II in the lungs by the action of ACE. ACE, or kininase II, also plays a key role in the kallikrein-kinin system by cleaving bradykinin to inactive peptides. In addition to the hormonal effects of circulating angiotensin II, all of the necessary components of the RAS exist in several organs and tissues, including the heart, kidneys, and vasculature. Figure 1. Pathophysiology of the RAS. SMC indicates smooth muscle cell. Angiotensin II exerts its actions in target organs and tissues by binding to both angiotensin II type 1 and 2 (AT1 and AT2) receptors, although adverse effects in humans seem to be mediated primarily by the AT1 receptor (Figure 1). In the kidney, angiotensin II causes sodium and water retention and efferent arteriolar vasoconstriction. Constriction of the systemic vasculature by angiotensin II causes hypertension, whereas coronary vasoconstriction may cause myocardial ischemia and arrhythmias. Angiotensin II–stimulated secretion of aldosterone by the adrenal cortex and arginine …

Is preventive medicine responsible for the increasing prevalence of heart failure?

Objective To investigate the effects of nicorandil (NIC) on patients with acute anterior myocardial infarction (AMI). Methods A retrospective study was performed on 121 cases of patients with acute anterior wall ST segment elevation myocardial infarction and receive emergency percutaneous coronary intervention (PCI), 101 cases of male, female 20 cases, aged (61.35±3.93) years old, ranging from 46 to 77 years, by using the method to stochastic indicator were randomly divided into conventional treatment group (n=61) and nicorandil group (n=60). Conventional treatment group receiving coronary atherosclerotic heart disease in patients with secondary prevention medicine, nicorandil group in the conventional treatment group on the basis of preoperative via coronary artery injection, can to 4 mg, postoperative oral 5 mg, three times a day, for six months, observed in two groups of patients in slow blood flow and the occurrence of no reflow, myocardial infarction, thrombolysis trial (TIMI) flow grade, serum myocardial hypersensitive troponin level and the occurrence of postoperative hospitalization for heart failure and arrhythmia, the occurrence of cardiac events (including recurrent myocardial infarction, congestive heart failure, rehospitalization, and all-cause death) in the two groups was observed 6 months after the operation.The occurrence of angina pectoris in the two groups during the treatment period was recorded. Results The 24 hours after emergency PCI, the level of hypersensitive troponin in nicorandil group [(4 407±809) pg/ml]was lower than that in the conventional group [(7 456±1 028) pg/ml], with statistically significant difference (P<0.05). The incidence of heart failure [6.6% (4/61)]in the nicorandil group was lower than that in the conventional group [20.0% (12/60)], and the incidence of arrhythmia [9.8% (6/61)]was lower than that in the conventional group [23.3% (14/60)], with statistically significant differences (P<0.05). The recurrence rate of angina pectoris in the nicorandil group [6.6% (4/61)]was lower than that in the conventional group [23.3% (14/60)], and the difference was statistically significant (P<0.05). Conclusion Continuous nicorandil therapy can reduce myocardial injury in patients with acute ST-segment elevation myocardial infarction, improve short-term therapeutic effect of acute ST-segment elevation myocardial infarction, and improve long-term cardiac function of patients, which is worthy of clinical application. Key words: Nicorandil; Acute myocardial infarction; Cardiac function; Angina pectoris; Hypersensitive troponin

iwan and co-investigators report in this issue of Circulation that the interval between onset of mitral E and annular early diastolic velocity (Ea) by tissue Doppler, T EϪEa , can be used to estimate left ventricular (LV) filling pressure in patients with mitral valve disease. 1 Garcia and colleagues were the first to report that the onset of Ea occurred 7.5Ϯ3.5 ms after peak mitral inflow velocity in 7 patients with restrictive cardiomyopathy, whereas Ea started 22Ϯ19 ms earlier than did E in the normal group. 2Subsequently, T EϪEa has been shown to correlate with the time constant of LV relaxation () demonstrated by Hasegawa and associates in their elegant animal experiment. 3With worsening of heart failure by rapid pacing, Ea progressively decreased in velocity and delayed in onset.Mitral E occurred coincidently with the termination of the early diastolic left arterial (LA) and LV pressure gradient at baseline and all stages of heart failure.In contrast, with increasing heart failure, Ea was progressively delayed after LA to LV pressure crossover, and T EϪEa was related to .Rivas-Gotz, Nagueh, and their associates also demonstrated that T EϪEa was prolonged after constriction of the circumflex coronary artery in dogs. 4In patients with heart failure, LV myocardial relaxation and compliance are decreased.

Part 7: The Era of Reperfusion