Use of Levosimendan as bridge therapy to surgical correction of post-infarction ventricular septal defect: a case report.

OBJECTIVE: Ventricular septal defect (VSD) is an uncommon but frequently fatal complication following acute myocardial infarction. In medically treated patients, mortality rates exceed 90%, while the surgical repair is associated with better outcomes, even though optimal surgical timing is still under debate. CASE REPORT: We present the case of a 78-years-old man with no previous remarkable cardiological history admitted to our Emergency Department with the diagnosis of anterior ST-elevation myocardial infarction and significant reduction of left ventricular ejection fraction. The emergency coronary angiography showed sub-occlusion of the left anterior descending coronary artery, treated with stent implantation. The post-procedural echocardiography unveiled the presence of an apical VSD with a large left-to-right shunt, significant right ventricular overload and dysfunction. An intra-aortic balloon pump (IABP) was positioned and, after Heart Team evaluation, a delayed surgical approach was planned. As a bridge to the intervention Levosimendan infusion was administered, on top of IABP support, and a significant improvement in bi-ventricular function and pressure profiles was obtained. Cardiac surgery was successfully performed 9 days after the admission without periprocedural complications. CONCLUSIONS: This unique case supports the use of Levosimendan as a valid pharmacological strategy for perioperative management of VSD.

Acute myocardial infarction interventional procedures: primary percutaneous coronary intervention versus facilitated percutaneous coronary intervention, rescue angioplasty, rescue excimer laser.

ST-elevation myocardial infarction is due to the occlusion of a coronary artery, mainly due to a rupture of an atherosclerotic plaque with superimposed thrombosis. The main therapeutic goal is to restore the blood flow within the culprit artery as quickly as possible. In this review we discussed the several approaches which have been employed to reach this target. Primary percutaneous coronary intervention (PCI) is considered the best treatment option, as it is associated to lower in-hospital mortality, reduced risk of reinfarction and stroke, lower rate of intracranial bleeding and ventricular rupture from myocardial hemorrhage compared with fibrinolytic therapy. Also, it is superior to facilitated PCI, i.e. immediate planned PCI after i.v. thrombolytic therapy administration, because of lower mortality, reinfarction rate, strokes and bleedings. Rescue PCI after failed thrombolysis was associated with a reduction of early severe heart failure and improved survival at 1 year, in patients with moderate to large infarctions, compared to conservative medical therapy, in a pooled analysis of 9 randomized trials, carried out in the balloon era. Also in the stent era, a meta-analysis of 5 randomized trials found a significant 36% reduction in the risk of 30-day mortality, a trend to lower risk of heart failure, although a marginally increased risk of thromboembolic stroke, in the rescue PCI arm. However, rescue PCI is not associated with a better long-term clinical outcome. Laser thrombectomy before PCI could be a useful additional strategy which might be compared to standard stenting in future randomized studies.

Myocardial infarction in isolated ventricular non-compaction: contrast echo and MRI.

We describe the case of an occasional discovery of isolated ventricular non-compaction in an adult recovered for an acute myocardial infarction, in which only the echocardiogram revealed an isolated ventricular non-compaction, confirmed by MRI: an unusual association between coronary artery disease and isolated ventricular non-compaction.

Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events.

BACKGROUND: A growing body of evidence suggests a role for inflammation in acute coronary syndromes. The aim of this study was to assess the role of proinflammatory cytokines, their time course, and their association with prognosis in unstable angina. METHODS AND RESULTS: We studied 43 patients aged 62+/-8 years admitted to our coronary care unit for Braunwald class IIIB unstable angina. In each patient, serum levels of interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6) (which represent sensitive markers of biologically active IL-1beta and tumor necrosis factor-alpha levels, respectively), and troponin T were measured at entry and 48 hours after admission. Troponin T-positive patients were excluded. Patients were divided a posteriori into 2 groups according to their in-hospital outcome: group 1 comprised 17 patients with an uneventful course, and group 2 comprised 26 patients with a complicated in-hospital course. In group 1, mean IL-1Ra decreased at 48 hours by 12%, and IL-6 diminished at 48 hours by 13%. In group 2, IL-1Ra and IL-6 entry levels were higher than in group 1 and increased respectively by 37% and 57% at 48 hours (P<0.01). CONCLUSIONS: These findings indicate that although they receive the same medical therapy as patients who do not experience an in-hospital event, patients with unstable angina and with complicated in-hospital courses have higher cytokine levels on admission. A fall in IL-1Ra and IL-6 48 hours after admission was associated with an uneventful course and their increase with a complicated hospital course. These findings may suggest novel therapeutic approaches to patients with unstable angina.

Intracellular neutrophil myeloperoxidase is reduced in unstable angina and acute myocardial infarction, but its reduction is not related to ischemia.

OBJECTIVES: This study sought to assess neutrophil activation in acute coronary syndromes and its relation to ischemic episodes. BACKGROUND: Neutrophil activation has been reported in unstable angina and acute myocardial infarction; however, it is not clear whether it is related exclusively to ischemia-reperfusion injury. METHODS: We measured the index of intracellular myeloperoxidase in 1) patients with unstable angina, myocardial infarction, variant angina and chronic stable angina and in normal subjects (protocol A); and 2) in patients with unstable angina and acute myocardial infarction during the first 4 days of the hospital period (protocol B). To assess whether neutrophil activation was triggered by ischemia, the myeloperoxidase intracellular index was analyzed before and after spontaneous ischemic episodes and before and after ischemia induced by an exercise stress test in 10 patients with chronic stable angina. In 11 patients with unstable angina, we also compared values of the myeloperoxidase intracellular index at entry with those after waning of symptoms. RESULTS: In protocol A, the myeloperoxidase intracellular index was significantly reduced in patients with unstable angina and acute myocardial infarction compared with patients with stable and variant angina and normal subjects (p < 0.01). In protocol B, the myeloperoxidase intracellular index did not change over time in patients with unstable angina and myocardial infarction. However, in 11 patients with waning symptoms, the myeloperoxidase intracellular index was significantly higher afer symptoms had waned (p < 0.05). In patients with unstable angina, 23 ischemic episodes were studied; no changes in the myeloperoxidase intracellular index were observed. In 10 patients with chronic stable angina and positive exercise stress test results, no significant differences in the myeloperoxidase intracellular index were observed after stress-induced ischemia. CONCLUSIONS: Our study confirms that neutrophils are activated in acute coronary syndromes but suggests that their activation may not be only secondary to ischemia-reperfusion injury.

Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty.

OBJECTIVES: We sought to investigate whether early and late outcome after percutaneous transluminal coronary angioplasty (PTCA) could be predicted by baseline levels of acute-phase reactants. BACKGROUND: Although some risk factors for acute complications and restenosis have been identified, an accurate preprocedural risk stratification of patients undergoing PTCA is still lacking. METHODS: Levels of C-reactive protein (CRP), serum amyloid A protein (SAA) and fibrinogen were measured in 52 stable angina and 69 unstable angina patients undergoing single vessel PTCA. RESULTS: Tertiles of CRP levels (relative risk [RR] = 12.2, p < 0.001), systemic hypertension (RR = 4.3, p = 0.046) and female gender (RR = 4.1, p = 0.033) were the only independent predictors of early adverse events. Intraprocedural and in-hospital complications were observed in 22% of 69 patients with high serum levels (>0.3 mg/dl) of CRP and in none of 52 patients with normal CRP levels (p < 0.001). Tertiles of CRP levels (RR = 6.2, p = 0.001), SAA levels (RR = 6.0, p = 0.011), residual stenosis (RR = 3.2, p = 0.007) and acute gain (RR = 0.3, p = 0.01) were the only independent predictors of clinical restenosis. At one-year follow-up, clinical restenosis developed in 63% of patients with high CRP levels and in 27% of those with normal CRP levels (p < 0.001). CONCLUSIONS: Preprocedural CRP level, an easily measurable marker of acute phase response, is a powerful predictor of both early and late outcome in patients undergoing single vessel PTCA, suggesting that early complications and clinical restenosis are markedly influenced by the preprocedural degree of inflammatory cell activation.

Enhanced inflammatory response in patients with preinfarction unstable angina.

OBJECTIVES: We assessed the extent and the time course of the acute phase response following myocardial cell necrosis and its relationship with the presence of preinfarction unstable angina (UA). BACKGROUND: Elevated levels of acute phase proteins have been reported in patients with UA and in patients with acute myocardial infarction (MI). METHODS: C-Reactive Protein (CRP), serum amyloid A protein (SAA) and interleukin-6 (IL-6) were measured in 36 patients with MI admitted within 3 h from symptoms onset. All patients had normal levels of creatine kinase and of troponin T on admission, rising above diagnostic levels within 6 to 12 h. Blood samples for CRP, SAA and IL-6 measurements were taken on admission, at 6, 24, 48, 72 h and at discharge. RESULTS: Twenty of the 36 patients studied presented an unheralded MI (Group 1); the remaining 16 patients had symptoms of unstable angina in the preceding 7 days (Group 2). Group 2 patients have much higher levels of CRP and SAA on admission (median values 8.8 vs. 3 mg/L and 28 vs. 3.4 mg/L, respectively, all p<0.001). Following the necrotic insult, despite similar infarct size and clinical signs of reperfusion, Group 2 patients had strikingly higher peaks of IL-6 (median values 85.2 vs. 19 pg/ml, p<0.05), CRP (50 vs. 31.4 mg/L, p<0.05) and SAA (228 vs. 45 mg/L, p<0.001). CONCLUSIONS: Our data demonstrated that the acute phase response is greatly enhanced in patients with preinfarction UA compared with those presenting with an unheralded MI. The significant differences in acute phase response observed in these two clinical presentations of MI indicate a major difference in their underlying pathogenetic components.

Usefulness of the addition of heart rate variability to Holter monitoring in predicting in-hospital cardiac events in patients with unstable angina pectoris.

Transient ischemia on Holter monitoring is a major determinant of outcome in unstable angina. In this study we investigated whether analysis of heart rate variability (HRV) may further improve the prognostic yield of Holter monitoring in this clinical setting. We performed 24-hour Holter monitoring in 75 patients with unstable angina (59 men, aged 62 +/- 9 years) within 12 hours of hospital admission. Number and duration of myocardial ischemic episodes, and both time domain and frequency domain HRV measures were obtained from Holter recordings. In-hospital major cardiac events (death or myocardial infarction) occurred in 7 patients (9%). Episodes of ST-segment depression on Holter monitoring were found in 6 of 7 patients (86%) with and in 26 of 68 patients (38%) without events (p <0.05). There were no differences between patients with or without events in both time domain (standard deviation [SD] of all normal RR intervals in the entire 24-hour electrocardiographic recording (SDNN), SD of the mean RR intervals for all 5-minute segments (SDANN-i), mean of SD of all RR intervals for all 5-minute segments (SDNN-i), percentage of differences between adjacent RR intervals >50 ms (pNN50), and square root of the mean squared differences of successive RR intervals) (RMSSD), and frequency domain (ultra low, very low, low, and high frequency) HRV indexes. However, the low-frequency/high-frequency (LF/HF) ratio was significantly higher in patients with cardiac events (2.12 +/- 1.4 vs 1.48 +/- 0.5, p = 0.01). Moreover, when considering only the 32 patients with myocardial ischemic episodes on Holter monitoring, the LF/HF ratio was again higher in the 6 patients with than the 26 patients without major cardiac events (2.45 +/- 1.5 vs 1.31 +/- 0.3, p <0.01). Multivariate logistic regression, including clinical and angiographic variables, showed that transient ischemia on Holter monitoring was the only independent determinant of outcome (odds ratio = 12.2, p = 0.03), with the LF/HF ratio being only slightly over statistical significance (odds ratio for 0.1 increments = 2.8, p = 0.08). Our data confirm that transient ischemia on Holter monitoring is a powerful predictor of cardiac events in unstable angina and indicates that an imbalance in cardiac autonomic tone toward a prevalence of sympathetic activity increases the risk of events in this group of patients.

Circadian variation of ventricular tachycardia in acute myocardial infarction.

Circadian rhythms have been described both for acute myocardial infarction (AMI) and sudden death. In this study the diurnal distribution of ventricular tachycardia (VT) in patients with AMI was analyzed. Ninety-four AMI patients with greater than or equal to 1 VT on Holter electrocardiographic monitoring who were not taking antiarrhythmic drugs were studied. Forty-seven patients had a recent AMI (group A) and 47 an old AMI (group B). Chronobiologic analysis was made by single cosinor method. There were 157 VTs (mean 1.67 VTs/patient, range 1 to 10) in the 94 patients: 70 in group A and 87 in group B. A significant circadian rhythm of VT was found in the total population with acrophase at 2:29 P.M. The hourly distribution of VT showed a tendency to bimodality, which seemed due to a different time of peak VT occurrence in group A (significant rhythm with acrophase at 4:40 P.M.) and group B (significant rhythm with acrophase at 12:39 P.M.). Thus, the hourly VT frequency in patients with AMI has a significant circadian variation with the highest occurrence in the awake hours, similar to the rhythms described for AMI and sudden death.

Incremental prognostic value of serum levels of troponin T and C-reactive protein on admission in patients with unstable angina pectoris.

Management of unstable angina is largely determined by symptoms, yet some symptomatic patients stabilize, whereas others develop myocardial infarction after waning of symptoms. Therefore, markers of short-term risk, available on admission, are needed. The value of 4 prognostic indicators available on admission (pain in the last 24 hours, electrocardiogram [ECG], troponin T, and C-reactive protein [CRP]), and of Holter monitoring available during the subsequent 24 hours was analyzed in 102 patients with Braunwald class IIIB unstable angina hospitalized in 4 centers. The patients were divided into 3 groups: group 1, 27 with pain during the last 24 hours and ischemic electrocardiographic changes; group 2, 45 with pain or electrocardiographic changes; group 3, 30 with neither pain nor electrocardiographic changes. Troponin T, CRP, ECG on admission, and Holter monitoring were analyzed blindly in the core laboratory. Fifteen patients developed myocardial infarction: 22% in group 1, 13% in group 2, and 10% in group 3. Twenty-eight patients underwent revascularization: 37% in group 1, 35% in group 2, and 7% in group 2 (p <0.01 between groups 1 or 2 vs group 3). Myocardial infarction was more frequent in patients with elevated troponin T (50% vs 9%, p=0.001) and elevated CRP (24% vs 4%, p= 0.01). Positive troponin T or CRP identified all myocardial infarctions in group 3. Only 1 of 46 patients with negative troponin T and CRP developed myocardial infarction. Among the indicators available on admission, multivariate analysis showed that troponin T (p=0.02) and CRP (p=0.04) were independently associated with myocardial infarction. Troponin T had the highest specificity (92%), and CRP the highest sensitivity (87%). Positive results on Holter monitoring were also associated with myocardial infarction (p=0.003), but when added to troponin T and CRP, increased specificity and positive predictive value by only 3%. Thus, in patients with class IIIB unstable angina, among data potentially available on admission, serum levels of troponin T and CRP have a significantly greater prognostic accuracy than symptoms and ECGs. Holter monitoring, available 24 hours later, adds no significant information.

Episodic activation of the coagulation system in unstable angina does not elicit an acute phase reaction.

The results of our study suggest that the acute phase response may be partly related to a yet unknown primary inflammatory component in unstable angina. Further studies are needed to elucidate the actual role of inflammation in unstable angina and its relation to activation of the coagulation system.

Reproducibility in circadian rhythm of ventricular premature complexes.

To evaluate the existence and reproducibility of a circadian rhythm of ventricular premature complexes (VPCs), 38 patients (mean age 57 +/- 17 years) with greater than or equal to VPCs/hour were studied with 24-hour electrocardiogram Holter monitoring. Nineteen patients had coronary artery disease and 19 had structurally normal hearts. A second Holter electrocardiogram was recorded in all patients from 2 to 47 days (mean 11) after the first. Chronobiologic analysis was made by single and mean cosinor methods. A significant and similar circadian rhythm of VPCs was found in the total sample both on the first (mesor 399, acrophase at 15:08, p less than 0.01) and the second day (mesor 306, acrophase at 14:47, p less than 0.05), with 2 main peaks, the first in the late morning and the second in the afternoon. However, only 18 patients (47%, group A) had a significant individual circadian rhythm of VPCs on both days, whereas 20 (53%, group B) did not have a significant rhythm in greater than or equal to 1 day. A high reproducibility of the circadian rhythm of VPCs was found in group A patients, with a difference of 2.1 +/- 1.8 hours between the acrophases of the 2 days, whereas the difference was 4.4 +/- 3.3 hours in group B patients (p less than 0.01). Among group A patients, 14 (78%) had a VPC rhythm with acrophase occurring during waking hours, whereas the acrophase of 4 (22%) occurred during the night. The reproducibility of the circadian rhythm of VPCs was not influenced by gender, presence of coronary disease, medical therapy, basal VPC number, or day-to-day variability of VPCs, although group A patients were older than group B patients (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Reversible left anterior descending artery spasm, prolonged cardiac arrest and left main thrombosis during a PTCA attempt of the circumflex artery.

The authors report a case of percutaneous transluminal coronary angioplasty of the circumflex artery complicated by occlusion of the non-diseased left anterior descending artery by spasm. During advanced cardiac life support, required for the subsequent cardiac arrest, intra-coronary nitrates and calcium antagonists were administered. After 45 minutes, the spasm resolved, but N probably as a result of prolonged blood stasis N a thrombus appeared in the left main artery. While attempting to stent the left main, the thrombus was mechanically dislodged, leaving the epicardial coronary tree free, with a good flow.

Altered urinary excretion of human kininase activity in acute myocardial infarction.

This study concerns the determination of levels of human urinary kininase excretion in acute myocardial infarction (AMI). The results obtained by a biological method show that there is a significant reduction of the enzymatic activity in patients affected by AMI in comparison with normals (6.4 +/- 0.4 ng of destroyed bradykinin/min. versus 164.4 +/- 31.4 ng; P less than 0.001), while urinary kallikrein excretion was close to normal values.

Rhythm of carnitine levels in serum and urine of normal subjects.

A study of the diurnal serum and urine levels of L-carnitine and acetylcarnitine was carried out in eleven healthy volunteers. No significant difference was found between the levels in the morning and in the afternoon, although a higher carnitinaemia was shown in the waking hours when the energy demands were higher.

[Blood catecholamines in liver cirrhosis]. / Le catecolamine ematiche nella cirrosi epatica.

Haematic concentrations of catecholamines were found to be higher in cirrhotic patients with ascites, than cirrhotic patients without ascites and controls. In compensated and decompensated cirrhosis, different forms of sympathetic nervous activity were observed. The high catecholamine values in cirrhotic patients and the activation of the renin angiotensin-aldosterone system suggest the use of beta-blockers to reduce sodium-water retention.

[Serum biliary acids in hepatic cirrhosis]. / Gli acidi biliari sierici nella cirrosi epatica.

Radioimmunological measurement of serum bile acids has shown that they increase in alcoholic cirrhosis of the liver. In normal subjects, the fasting value of serum bile acids averaged 2.5 +/- 0.41 microM/l, whereas in cirrhotics it was 37.8 +/- 7.9 microM/l (p < 0.001). This technique has proved more specific than routine liver function tests. Measurement of fasting serum bile acids is a sensitive, specific, reproducible index of liver bile function. A quality investigation of primary and secondary bile acids requires the adoption of more sensitive techniques which are not, however, readily adaptable to routine use.

[Lactic acidosis associated with fenformin therapy]. / Acidosi lattica associata a terapia con fenformina.

Irreversible lactic acidosis occurred in two phenformin-treated diabetics. In the first case, blood creatinine was 3 mg % ml, arterial blood pH was 7,12 and ketostix was negative; in the second case, blood creatinine was 1,3 mg% ml, arterial blood pH was 7,22 and ketostix was negative. Diabetic patients to be treated with phenformin must always be carefully selected and this treatment should be reserved for cases where there is a precise indication. Lactic acidosis may occur even in the presence of almost normal serum creatinine concentrations.

[Plasma insulin and GH during oral glucose load in liver cirrhosis]. / L'insulina ed il GH plasmatici in corso di carico orale di glucosio nella cirrosi epatica

Blood sugar, insulin and GH values were examined in two groups of cirrhosis of the liver patients, with and without ascites, after the administration of 100 g glucose per os. No significant differences between the two groups were observed. Insulin values were higher than those in the controls, with a pattern similar to that noted in subjects with chemical diabetes. GH values were higher than in normal subjects and secretion was not suppressed.

[The association of diabetic disease with Friedreich's disease in members of the same family]. / L'associazione della malattia diabetica col morbo di Friedreich in componenti dello stesso nucleo famigliare

Friedreigh's disease is only rarely associated with diabetes mellitus and only few cases are to be found in the literature, especially as regards siblings. Three cases of this association in members of two different families are reported. Two of the patients died from cardiovascular complication; the third case is that of a 32-yr-old woman who was able to complete a pregnancy. The pathogenesis of the association is discussed and a number of theories are put forward. The most generally accepted genetic hypothesis makes it possible to explain under a common metabolic denominator neurological disturbances and those in other systems. The association is not a purely casual event but is perhaps dependent on either two different genes or on a single gene with pleitropic effect. Heart signs are frequent in Friedreich's disease and brief mention is made of these.