The Reduction of Mortality in Acute Myocardial Infarction: From Bed Rest to Future Directions.

Despite the reduction of mortality secondary to cardiovascular diseases observed in the last decades, ischemic heart disease remains the most common cause of death worldwide. Among the spectrum of ischemic heart disease, myocardial infarction accounts for most deaths. Since the introduction of the coronary care units in the 1960s, and until the latest antithrombotic drugs, myocardial infarction survival improved by 40-50%. However long-term mortality after myocardial infarction has not improved as short-term mortality. Moreover, the decline of mortality has apparently reached a "plateau" in the past 15 years. In this review we describe the steps of the improvement in ischemic heart disease mortality, from the bed rest to the possible future of treating microcirculation. In fact, coronary artery disease is not only a disease of large vessels that can be visualized with coronary angiography. The small network of pre-arterioles and arterioles that supply the myocardium can be also affected in ischemic heart disease. Thus, despite the introduction of effective recanalization strategies for epicardial coronary arteries such as thrombolysis and, more recently, primary percutaneous intervention, some patients may not achieve effective myocardial reperfusion due to microvascular dysfunction or damage after myocardial myocardial infarction. This phenomenon is named no reflow. We believe that no reflow, through the incomplete reperfusion that can account for a higher rate of adverse event in the follow up, should be regarded as one of the open issues in the modern treatment of myocardial infarction.

Long-Term Contrast Echocardiography and Clinical Follow-Up after Percutaneous Closure of Patent Foramen Ovale Using Two Different Atrial Septal Occluder Devices.

INTRODUCTION: Percutaneous patent foramen ovale (PFO) closure by means of a septal occluder device (SOD) is a well-known therapeutic strategy for the secondary prevention of paradoxical embolic neurological events. The aim of this study was to provide long-term echocardiographic and clinical follow-up data on patients who had undergone percutaneous PFO closure with 2 different SOD. METHODS: We selected 2 groups of patients treated with 2 different SOD: Group A: 52 patients with an Amplatzer(®) PFO Occluder and Group B: 49 patients with a Figulla Flex(®) device. All patients underwent follow-up Bubble Test Transthoracic Echocardiography (BTTE) and clinical examination. The results were compared with those recently reported in a group of patients with similar characteristics, but that had been treated conservatively, which acted as a control group. RESULTS: The mean follow-up after PFO closure was 53 months. The Amplatzer(®) PFO Occluder and the Figulla Flex were used in 52 (51.5%) and 49 (48.5%) of patients, respectively. We found no significant difference in the rate of effective PFO closure between the devices: Amplatzer 91.4%, Figulla 93.9% (P = 0.71). One patient (1.0%) suffered a recurrent neurologic event. BTTE was positive (BTTE+) in 8 patients (8%), 5 with an Amplatzer, and 3 with a Figulla device (P = 0.516). Only 1 patient with BTTE+ had a recurrent TIA (12.5%). No significant relationship was found between device dimensions and BTTE+ (P = 0.062). In the control group (163 patients), the recurrence of neurologic events was 9.2% (15 events), that was significantly higher in respect to the patients who had undergone percutaneous closure of the PFO. CONCLUSIONS: Percutaneous PFO closure was associated with a remarkably low risk of recurrent embolic neurological events, and no long-term device-related major complications. No statistically significant difference emerged between the 2 different SODs regarding BTTE positivity. Long-term follow-up showed that the recurrence of neurological events has been significantly higher in the group treated in a conservative way.

Asymmetric and Symmetric Dimethylarginine and Sympathetic Nerve Traffic after Renal Denervation in Patients with Resistant Hypertension.

BACKGROUND AND OBJECTIVES: The plasma concentration of the endogenous inhibitor of nitric oxide synthase asymmetric dimethylarginine (ADMA) associates with sympathetic activity in patients with CKD, but the driver of this association is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this longitudinal study (follow-up: 2 weeks-6 months), repeated measurements over time of muscle sympathetic nerve activity corrected (MSNAC), plasma levels of ADMA and symmetric dimethylarginine (SDMA), and BP and heart rate were performed in 14 patients with drug-resistant hypertension who underwent bilateral renal denervation (enrolled in 2013 and followed-up until February 2014). Stability of ADMA, SDMA, BP, and MSNAC over time (6 months) was assessed in two historical control groups of patients maintained on stable antihypertensive treatment. RESULTS: Time-integrated changes in MSNAC after renal denervation ranged from -40.6% to 10% (average, -15.1%), and these changes were strongly associated with the corresponding changes in plasma ADMA (r= 0.62, P=0.02) and SDMA (r=0.72, P=0.004). Changes in MSNAC went along with simultaneous changes in standardized systolic (r=0.65, P=0.01) and diastolic BP (r=0.61, P=0.02). In the historical control groups, no change in ADMA, SDMA, BP, and MSNAC levels was recorded during a 6-month follow-up. CONCLUSIONS: In patients with resistant hypertension, changes in sympathetic activity after renal denervation associate with simultaneous changes in plasma levels of the two major endogenous methylarginines, ADMA and SDMA. These observations are compatible with the hypothesis that the sympathetic nervous system exerts an important role in modulating circulating levels of ADMA and SDMA in this condition.

Automated carbon dioxide digital angiography for lower-limb arterial disease evaluation: safety assessment and comparison with standard iodinated contrast media angiography.

INTRODUCTION: Carbon dioxide (CO2) has been validated as a contrast agent in a large series of studies. A particular advantages of CO2 over iodinated contrast medium (ICM) is the absence of nephrotoxicity and allergic reactions. One of the limitations of CO2 angiography is the difficulty of CO2 manual injection due to its compressibility. The manual gas injection does not permit optimal control of the gas output. Development of an automated CO2 injector has overcome these problems. AIM: This study compares the feasibility, safety, and diagnostic accuracy of automated CO2 digital subtraction angiography (DSA) in comparison with ICM-DSA in the evaluation of critical limb ischemic (CLI) patients. METHODS: We performed DSA with both CO2 and ICM on 40 consecutive CLI patients and directly compared the two techniques. Sixteen females and 24 males participated in the study (mean age, 71.7 years). We assessed the diagnostic accuracy of CO2 in identifying arterial stenosis in the lower limb, with ICM-DSA used as the gold standard. RESULTS: The overall diagnostic accuracy of CO2-DSA was 96.9% (sensitivity, 99.0%; specificity, 96.1%; positive predictive value, 91.1%; negative predictive value, 99.6%). Tolerable minor symptoms occurred in 3 patients. No allergic reactions or significant decline in renal function were observed in patients receiving the CO2 injection. CONCLUSION: Carbon dioxide DSA is a valuable and safe alternative to traditional ICM-DSA for evaluating CLI patients. This modality should be considered as the standard choice for CLI patients undergoing angiographic evaluation who are known to have renal insufficiency or contrast allergy.

The prognostic role of troponin I elevation after elective percutaneous coronary intervention.

OBJECTIVES: To assess the prognostic role of isolated troponin I (TnI) elevation after elective percutaneous coronary intervention (PCI) in patients with stable coronary artery disease. BACKGROUND: The prognostic role of minor troponin elevation after PCI is controversial. METHODS: A total of 1532 consecutive patients who underwent elective PCI were included. Follow-up data were obtained for 1432 of 1532 (93.4%) patients. The events taken into account in the follow-up included total mortality, cardiac death, hospitalization for acute myocardial infarction and/or unstable angina. RESULTS: The following variables were identified as predictive of major adverse cardiac events (MACE) by univariate analysis: age 75 years at least (P = 0.012), ejection fraction less than 50% (P = 0.001), prior myocardial infarction (P = 0.031) and TnI 1.0 ng/ml at least after PCI (P = 0.04). The Cox-regression model identified the TnI elevation after PCI, the older age and the ejection fraction as independent predictors of MACE during follow-up (TnI: P = 0.042; older age: P = 0.001; ejection fraction: P = 0.003). In a subgroup of patients with preserved ejection fraction, the incidence of MACE was significantly higher in those with TnI of at least 1.0 ng/ml at least than in the ones with TnI less than 1.0 ng/ml, with the highest incidence among the older cohort. The multivariate analysis confirmed the TnI elevation 1.0 ng/ml at least after PCI and the older age as predictors of MACE. CONCLUSION: This study documented that in clinically stable patients, minor TnI elevations after elective PCI are independent predictors of MACE during follow-up, as are older age and reduced ejection fraction. Additionally, TnI elevation was a predictor of MACE during follow-up in a subset of patients with preserved ejection fraction. The combination of TnI elevation and older age confers the highest risk of MACE.

[Drug-eluting stents in non-coronary arteries]. / Gli stent medicati nei distretti arteriosi non coronarici.

According to the available literature, drug-eluting stents (DES) are used mainly in coronary arteries. However, DES are used in non-coronary districts as well. The indication for DES implantation in non-coronary arteries is the same as that in the coronary circulation that is to prevent restenosis. Although data from both controlled studies and observational reports do exist, the use of DES in the non-coronary circulation is very limited and is not comparable with that for the treatment of coronary artery disease. The most important factors one has to consider before DES implantation in non-coronary arteries are histologic features, blood flow characteristics and compressive extrinsic forces. Further studies on larger populations are warranted to define the ideal combination stent/drug and the clinical indications for the correct use of DES in non-coronary vascular districts.

Stress-induced QTc-interval shortening as an ancillary marker of ischemia in patients with complete left bundle branch block.

BACKGROUND: In patients with left bundle branch block (LBBB), ischemia-induced repolarization changes associated with QTc-interval shortening may be recorded during coronary angioplasty. We aimed to assess whether these repolarization changes may be predictive of severe coronary artery disease in patients with LBBB. METHODS: Fifty noninfarcted LBBB patients underwent dipyridamole stress test and coronary angiography for chest pain. To localize the site of ischemia, we considered four groups of conventional ECG leads (V1-V2-V3; V4-V5-V6; aVL-I; III-aVF-II), exploring the anteroseptal, lateral, high-lateral, and inferior left ventricular walls. ST-T changes and QTc intervals were estimated at rest and peak stress, lead by lead, in each group of leads and the fractional percentage difference between rest-stress QTc intervals ([DELTA]QTc) was calculated. A [DELTA]QTc greater than -10% was used to define significant QTc-interval shortening. Coronary stenosis of more than 70% and more than 90% were considered 'significant' and 'severe'. RESULTS: According to dipyridamole stress test response, two groups were identified: group I (35 patients) with dipyridamole-induced ischemia and group II (15 patients) without dipyridamole-induced ischemia. The wall motion score index at peak stress (compared with resting wall motion score index) was significantly higher in group I (1.98 +/- 0.13 vs. 1.28 +/- 0.08, P < 0.0001) than in group II (1.36 +/- 0.18 vs. 1.25 +/- 0.08, P = 0.296). The patients of group I showed a significant QTc-interval shortening ([DELTA]QTc = -16.9 +/- 3.9%), whereas this did not happen in patients of group II ([DELTA]QTc = +8.8 +/- 2.4%, P < 0.0001). The patients of group I also had a more severe stenosis in the vessel related to the stress-induced dyssynergic area (I = 90.5 +/- 9.5 vs. II = 34.3 +/- 31.1%; P < 0.0001). CONCLUSION: In patients with LBBB, stress-induced pseudonormalization pattern, associated with QTc-interval shortening, allows the identification of cardiac areas supplied by severely stenosed coronary arteries.

Multislice computed tomography for the evaluation of coronary bypass grafts and native coronary arteries: comparison with traditional angiography.

BACKGROUND: Multislice computed tomography (CT) is a promising new noninvasive technique for the detection of atherosclerotic disease within a vessel's wall. The present study was designed to assess the diagnostic accuracy of 64-slice CT in detecting graft disease and in the evaluation of native vessels distally to the grafts. METHODS: Forty consecutive patients with previous coronary artery bypass underwent both invasive coronary angiography and 64-slice CT. The CT data were acquired over 7-12 s period during a single-breath hold using the Smartprep technique. Images were reconstructed using the retrospective modality on a synchronized ECG in a time frame of between 40 and 80% of the R-R interval. RESULTS: A total of 118 grafts were investigated (80 vein and 38 arterial conduits). At CT, 31/38 arterial grafts were classified as patent and free from significant lesions, whereas seven appeared diseased (five complete occlusion and two significant stenoses along the body of the graft). Out of 80 vein grafts, 52 appeared free of disease and 28 diseased (23 total occlusion and five critical stenosis). An absolute concordance between CT and angiographic findings was documented for all arterial and venous grafts (100% diagnostic concordance). The accuracy of 64-slice CT in the assessment of distal run-off arteries was 90%. CONCLUSION: The 64-slice CT detected with very high accuracy the presence of diseased arterial and vein grafts. Moreover, an optimal diagnostic accuracy was also documented in the appraisal of native vessels distal to the graft anastomoses. On the basis of these results, 64-slice CT can be proposed for the study of patients after coronary artery bypass and may represent an effective screening technique to select those patients with indications of new revascularization.

Effects of physical training on cardiovascular control after heart transplantation.

BACKGROUND: Exercise performance in heart-transplanted patients increases with respect to pre-transplantation but remains subnormal, and it does not improve with time after surgery. Possible causes include persisting denervation, and sympathetic vasoconstriction inducing functional vascular abnormalities that prevent adequate increase in blood flow to the exercising limbs. We tested the effects of physical training on baroreceptors-mediated control of heart rate and blood pressure in recently heart-transplanted subjects. METHODS: Patients were randomly allocated to physical training (n=13, 30 min cycling at 60-70% of peak oxygen consumption for 5 days/week for 6 months) or to control (n=11). Upright exercise test to exhaustion was performed at the beginning of the study after 3 and 6 months. Reflex changes in RR interval and blood pressure in response to sinusoidal neck suction (6 and 12 cycles/min 0 to -30 mm Hg swing) were considered as evidence of reinnervation and baroreflex control of blood pressure, respectively. RESULTS: After 6 months peak oxygen consumption (p<0.001), exercise time (p<0.01) and workload (p<0.01) increased in trained patients. Before training RR interval and blood pressure were not modified by neck suction. After physical training systolic (p<0.01) and diastolic blood pressure decreased, RR interval and blood pressure could be modulated (p<0.05) by slow (6 cycles/min) neck suction, indicating initial cardiac sympathetic reinnervation and restored sensitivity to autonomic modulation on the arteries. No changes were observed in controls. CONCLUSIONS: Physical training improved exercise performance and the control exerted by the autonomic nervous system through the sympathetic nerves at both cardiac and vascular level.

Protective role of chronic statin therapy in reducing myocardial damage during percutaneous coronary intervention.

OBJECTIVE: Percutaneous coronary intervention (PCI) is frequently associated with troponin I (TnI) elevation. Experimental studies suggest that statins may reduce ischaemia-reperfusion myocardial injury. The study objective was to verify whether chronic treatment with statins might reduce the occurrence and the extent of periprocedural myocardial damage in patients undergoing PCI. METHODS: Five hundred and fifty-two consecutive patients undergoing PCI were included: 279 were not on statins before PCI, 273 were on statins. TnI levels >or= 0.3 ng/ml were considered indicative of myocardial injury. RESULTS: Statin-treated patients had a higher prevalence of hyperlipidaemia, previous myocardial infarction, and revascularization procedures. Coronary angiography also documented a higher prevalence of multivessel disease. No difference between the two groups was observed regarding the PCI-treated vessel, type of lesions, use of stents and of anti-IIb/IIIa inhibitors. Patients on statins showed the lowest incidence of TnI >or= 0.3 ng/ml (29 vs. 48%, P = 0.00001) and of creatine kinase-MB elevation (7 vs. 12%, P = 0.04). The mean peak TnI levels were significantly lower in patients on statins (1.07 +/- 3.8 vs. 2.73 +/- 12.3, P = 0.00006). Multivariate analysis identified preprocedural statin therapy as the only independent negative predictor of postprocedural abnormal TnI levels (odds ratio = 0.52; 95% confidence intervals 0.34-0.79; P = 0.003). CONCLUSIONS: This study shows that chronic therapy with statins reduces the incidence of periprocedural myocardial damage after PCI. The beneficial effect of statins was independent of either the most important clinical and angiographic characteristics or the use of other cardiovascular drugs including beta-blockers. These data support the specific cardioprotective role of statins.