Increase In Myocardial Oxygen Demand Research Articles

Levosimendan versus dobutamine in acute heart failure: Insight into short and long term mortality

Acute decompensated heart failure (ADHF) leads to substantial mortality. Levosimendan, a calcium sensitizer improves myocardial contractility without increase in myocardial oxygen demand. However, there is lack of local data to support usage.

Perioperative infarction and myocardial injury: risk factors, mechanisms of development and clinical and epidemiological features

Тhe concept, risk factors, mechanisms, clinical and epidemiological, and angiographic features of perioperative ischemic injury and myocardial infarction were considered. Perioperative myocardial infarction is one of the most common complications (up to 3.6%) in non-cardiac surgical interventions and is characterized by high in-hospital mortality, reaching 25%. Most patients with this pathology (up to 65%) do not have typical symptoms of myocardial ischemia due to anesthesia and sedation. Pathogenetic mechanisms of perioperative myocardial infarction development continues to be actively studied. A critical increase in myocardial oxygen demand is indicated as the leading cause in some studies. Angiography reveals rupture of the coronary plaque and atherothrombosis in more than half of patients, according to other data. These contradictions point to the need for further epidemiological studies using coronary angiography with a focus on risk factors and triggers of this complication. In addition, the concept of perioperative myocardial injury in recent years has been formulated in the scientific literature. This is understood as ischemic damage that occurs in the first 30 days after surgery. Recent studies have shown that it can occur in 16% of surgical patients and is associated with a 6-fold increase in mortality within 1 month after surgery and a 2.5-fold increase within a year. It is important that perioperative myocardial injury does not include cases of non-ischemic etiology myocardial injury, for example, due to pulmonary embolism, sepsis, or electrical cardioversion. Thus, the assessment and understanding of risk factors for the development of perioperative myocardial ischemia is of great practical importance in optimizing the patient selection and preparation for surgical treatment.

Pyridine nucleotide redox potential in coronary smooth muscle couples myocardial blood flow to cardiac metabolism

Adequate oxygen delivery to the heart during stress is essential for sustaining cardiac function. Acute increases in myocardial oxygen demand evoke coronary vasodilation and enhance perfusion via functional upregulation of smooth muscle voltage-gated K+ (Kv) channels. Because this response is controlled by Kv1 accessory subunits (i.e., Kvβ), which are NAD(P)(H)-dependent aldo-keto reductases, we tested the hypothesis that oxygen demand modifies arterial [NAD(H)]i, and that resultant cytosolic pyridine nucleotide redox state influences Kv1 activity. High-resolution imaging mass spectrometry and live-cell imaging reveal cardiac workload-dependent increases in NADH:NAD+ in intramyocardial arterial myocytes. Intracellular NAD(P)(H) redox ratios reflecting elevated oxygen demand potentiate native coronary Kv1 activity in a Kvβ2-dependent manner. Ablation of Kvβ2 catalysis suppresses redox-dependent increases in Kv1 activity, vasodilation, and the relationship between cardiac workload and myocardial blood flow. Collectively, this work suggests that the pyridine nucleotide sensitivity and enzymatic activity of Kvβ2 controls coronary vasoreactivity and myocardial blood flow during metabolic stress.

The Role of Coronary Artery Disease in Demand Mediated Myocardial Infarction: A Retrospective Study from a Community Hospital

Type 2 Myocardial Infarction (T2MI) is an increasingly recognized clinical entity due to the availability of highly sensitive troponin assays for patients admitted due to common medical diagnoses. However, there is little epidemiological data on the significance and long-term prognosis of T2MI, which occurs secondary to an increase in myocardial oxygen demand and/or a decrease in myocardial blood flow. Arrhythmia, hypoxia, and sepsis are the major etiologies for T2MI. Therefore, sepsis was the identified area of interest for the study giving how common it is in a community hospital. We studied the cardiac workup of patients with elevated troponin in the context of sepsis due to acute medical illness to find out the prevalence of obstructive coronary artery disease (CAD) in this population. In this two-year retrospective, descriptive study, electronic medical records (EMR) were reviewed for all patients aged 18 years and older admitted to a single community teaching hospital with a diagnosis of sepsis and elevated troponin I (> 0.07 ug/L). The primary outcome was the presence of obstructive CAD. The secondary outcome was time to peak serum troponin. Of 222 patients, 40 patients underwent invasive or/and noninvasive cardiac testing for CAD. The study revealed 30% of patients admitted with T2MI due to sepsis have underlying obstructive coronary artery lesions. Troponin rose slower in patients with T2MI with underlying obstructive CAD. Pneumonia was the most common underlying cause of sepsis in both groups. Given the considerable prevalence of underlying flow-limiting coronary artery lesions, it may be advisable to evaluate for obstructive CAD sooner than later, during the index hospitalization, when patients developed elevated troponin secondary to sepsis.

Surgical repair of coronary artery ostial stenosis in patients with Williams and elastin arteriopathy syndromes

ObjectivePatients with Williams and elastin arteriopathy syndromes often have similar cardiac phenotypes characterized by supravalvar aortic stenosis (SVAS), peripheral pulmonary artery stenosis (PPAS), and coronary artery ostial stenosis (CAOS). SVAS and/or PPAS result in a marked increase in myocardial oxygen demand, whereas CAOS may limit myocardial oxygen supply. This combination predisposes to myocardial ischemic events and sudden cardiac arrest. The purpose of this study was to review our experience with the surgical repair of CAOS in patients with Williams and elastin arteriopathy syndromes. MethodsThis was a retrospective review of 16 patients with Williams (n = 11) or elastin arteriopathy (n = 5) who underwent surgical repair of CAOS as a concomitant procedure with SVAS and/or PPAS repair. Eleven patients had moderate or severe SVAS, and 10 had PPAS. The median age at surgery was 9 months (range, 3-108 months). ResultsSeven patients had repair of the left main and right coronary ostia, 6 the left main, and 3 the right coronary ostium. Median duration of aortic crossclamp was 56 minutes and cardiopulmonary bypass time was 454 minutes. The median SVAS gradient decreased from 70 to 12 mm Hg and pulmonary artery pressure decreased from 120 to 30 mm Hg. There was 1 operative mortality (6%). The remaining 15 patients were discharged from the hospital and are alive at a median of 17 months' follow-up. ConclusionsThe data demonstrate that patients with Williams and elastin arteriopathy syndromes presenting with SVAS and/or PPAS plus CAOS can undergo successful repair of all hemodynamic issues simultaneously.

Impaired Oxygenation of the Right Ventricle during Development of Pulmonary Hypertension in Swine is not due to Loss of Nitric Oxide

BackgroundPulmonary hypertension (PH) increases workload of the right ventricle (RV), resulting in RV hypertrophy. Eventually the RV is unable to cope with the high afterload, resulting in RV failure and death. The transition of RV hypertrophy to failure is incompletely understood, but we have recently shown that myocardial oxygen supply did not increase commensurate with the increase in myocardial oxygen demand. This mismatch between oxygen supply and demand is exacerbated during physical activity when workload and hence oxygen demand increases. Here, we aim to investigate whether the contribution of the vasodilator nitric oxide (NO) and/or the vasoconstrictor endothelin (ET) to regulation of right ventricular coronary blood flow (RV‐CBF) is impaired in swine with PH.MethodsPH was induced by banding of the confluent of the inferior pulmonary vein in juvenile swine (N=5), while 5 healthy swine served as controls. Swine were chronically instrumented to measure pressure in the RV, pulmonary artery, left atrium and aorta, and right coronary blood flow (RV‐CBF) rest and during graded treadmill exercise. Exercise was performed in the presence and absence of eNOS‐inhibition or ET‐receptor blockade 12 weeks after pulmonary vein banding (PVB).ResultsPVB resulted in PH as evidenced by an increase in pulmonary artery pressure (PVB: 39±3 mmHg, CON: 21±1 mmHg, both P<0.05) that was accompanied by RV hypertrophy (Fulton index PVB: 0.58±0.02, CON: 0.44±0.02, P<0.05). The relation between myocardial oxygen supply (RV‐CBF*arterial oxygen content) and myocardial work (arterial elastance, pulmonary artery pressure/SV) rotated downward in PVB. However, despite increased plasma ET‐levels (PVB:8.8±0.5 pg/ml CON: 6.7±0.5 pg/ml, P<0.05), ET‐receptor blockade did not alter the relation between myocardial oxygen delivery and myocardial work. Conversely, eNOS‐inhibition resulted in a downward rotation of this relation that was more pronounced in PVB as compared to CON.ConclusionPH leads to a mismatch between myocardial oxygen supply and demand. This mismatch is not influenced by ET‐receptor blockade and is aggravated by eNOS‐inhibition, suggesting that NO plays an important role in maintaining RV‐perfusion particularly during exercise.

The effect of patent ductus arteriosus on coronary artery blood flow in premature infants: a prospective observational pilot study

ObjectiveTo compare coronary flows between premature infants with and without hemodynamically significant patent ductus arteriosus (hsPDA) and to determine if coronary flow is influenced by medical PDA treatment.DesignProspective, observational pilot study. Forty-three infants <32 weeks gestation underwent echocardiography when routinely indicated. Study group included infants with hsPDA requiring treatment. Comparison groups included infants with nonsignificant PDA and infants without PDA.ResultsThe study group (n = 13), compared with the comparison groups with nonsignificant PDA (n = 12) and without PDA (n = 18) had higher troponin levels (p = 0.003 and 0.004, respectively). In infants with hsPDA compared with infants with no PDA there was a significant increase in myocardial oxygen demand and decrease in left main coronary artery flow, with nonsignificant increase in cardiac output.ConclusionsDecrease in coronary artery flows and higher troponin values may suggest a “steal effect,” not allowing to meet the elevated myocardial oxygen demand in infants with hsPDA.

Predictors of the development of cardiac arrhythmias in women after induction of superovulation in vitro fertilization

The article presents the results of a clinical and instrumental examination of 80 healthy women (average age 32,313,57 years) in order to assess the heart rhythm disturbances after induction of superovulation duringin vitrofertilization. All women were examined twice before and after induction of superovulation during extracorporeal fertilization. Clinical and instrumental examination included: electrocardiography at rest; echocardiography; 24-hour ECG monitoring with heart rate variability analysis; 24-hour blood pressure monitoring. Induction of superovulation is associated with a significant increase in mean daily HR max (р0,01), and consequently with an increase in myocardial oxygen demand. It has been established that induction of superovulation contributes to the development of supraventricular arrhythmias (р0,01) and an increase in episodes of apnea/hypnea (р0,01). Regression analysis revealed predictors of supraventricular arrhythmias after induction of superovulation, including adverse circadian heart rate profile, adverse circadian blood pressure profile, impaired autonomic regulation of heart activity (р0,01). It was shown that the appearance of rhythm disturbances is associated with both the initial functional state of the cardiovascular system and its response to the induction of superovulation. It was established a correlation between the estradiol concentration and the increase of daily average heart rate after induction of superovulation (r=0,30,р0,05), apnea/hypnea index after induction of superovulation (r=0,34,р0,05). Conclusion. Superovulation induction may exacerbate existing chronic cardiovascular diseases. Due to the adverse effect of superovulation induction on the daily heart rate profile, women need to evaluate the functional state of the cardiovascular system duringinvitrofertilization planning. This will prepare the woman for the upcoming procedure and avoid adverse reactions from the cardiovascular system in response to stimulation of superovulationin vitrofertilization.

Arterial hypertension with comorbid chronic obstructive pulmonary disease: relationship between tolerance to physical exercise and structural and functional state of the heart.

The aim of the study was to establish the relationship between tolerance to exercise, oxygen saturation, and structural and functional cardiac status in patients with hypertension in combination with COPD. This study included 120 patients with primary arterial hypertension of stage I-II, grade 1, 2, and 3 in combination with COPD of grades 2 and 3 and clinical groups A, B, C, D, consisting group 1; group 2 – 30 patients with primary hypertension, and group 3 – 30 patients with COPD; group 4 – 30 practically healthy people representative by age and sex. Research methods included general clinical examination (collection of complaints, anamnestic data) and instrumental research methods: electrocardiography (ECG), echocardiography, measurement of ambulatory blood pressure (BP) profile (ABPM), spirometry, pulsoxymetry (SpO2), 6-minutes walking test (6MWT). On examination of 120 patients with stage I-II, grade 1 hypertension was established in 19 (15.8%), grade 2 was in 83 (69.2%) and grade 3 was in 18 (15%) patients, respectively. COPD in clinical group A was diagnosed in 10 (8.3%), B – in 51 (42.5%), C – in 18 (15%) and D - in 41 (34.2%) patients, respectively. The most common was AH stage 2 with COPD in clinical group B – 35 (29.2%) cases and D – 31 (25.8%) cases. The 24-hour average systolic BP (SBP) in patients of the main group was 165 [144;178] mmHg, and the diastolic BP (DBP) was 103 [94;111] mmHg. The daytime average SBP was 160 [140;180] mmHg, and the DBP was 105 [93;117] mmHg accordingly. The night-time average SBP was 165 [155;175] mmHg, DBP – 100 [95;105] mmHg, heart rate (HR) – 83 [76;88] minutes, respiration rate (RR) – 21 [19;24] minutes. Decreases in index of chronotropic reserve (ICR) and the index of inotropic reserve (IIR) and load index indicate an increase in myocardial oxygen demand during exercise. There was an inverse correlation of IIR with SBP at rest (r= –0.42; p˂0.05) and a direct correlation with age (r=0.28; p˂0.05), which is significantly different from the control group. A direct correlation was found between the double product (DP) before and after exercise (r=0.43; p˂0.05), which indicated an increase in consumption of oxygen by the myocardium. We found a direct correlation between left atrium (LA) and the ratio of expiratory volume per 1 sec (FEV1) to the forced lung capacity (FEV) – FEV1/FVC (r=0.32; p˂0.05), which indicates the effect of the severity of bronchial obstruction on the level of left ventricular (LV) overload in patients with hypertension combined with COPD. The inverse correlation between thickness of the posterior wall of the LV (RVWT) and FEV1/FVC (r= -0.32; p˂0.05) indicates the contribution of disorders of bronchial patency and intrathoracic pressure with the level of BP to the development of concentric remodeling and LV hypertrophy. The inverse correlation between SV and COPD Assessment Test (CAT) (r= -0.32; p˂0.05) indicates an additional effect of COPD clinical severity on central hemodynamics in patients with hypertension. This relationship between the ventilatory and hemodynamic parameters is confirmed by the inverse correlation of HR and FVC (r= –0.33; p˂0.05)), left ventricular internal dimension (LVEDD) of LV and CAT (r= –0.24; p˂0.05)), stroke volume (SV) and Modified British Medical Research Questionnaire (mMRC) (r= –0.42; p.00.05), CAT and pack years (r=0.33; p˂0.05), inverse correlation between CAT and mMRC and FEV1, FVC and FEV1/FVC (r= -0.40;p˂0.05 and r= -0.45; p˂0.05), respectively. Linear regression analysis showed that changes in SV LV, LVEDD and SpO2 were dependent predictors of patient’s worsening state according to CAT (p˂0.05). The direct correlation was established between the desaturation (ΔSpO2) and ΔDP (r=0.48) and the inverse of ΔSBP (r= -0.29), 6MWT (r= -0.45), ICR (r= -0.34) and IIR (r= -0.29), which indicates a pronounced effect of hypoxemia on hemo­dynamics in patients with hypertension in combination with COPD. Comprehensive determination of cardiorespiratory reserve by 6-minute walk test, pulse oximetry and ambulatory blood pressure monitoring in patients with hypertension in combination with COPD makes it possible to establish disadaptation of the body to physical activity due to hypoxemia, decrease in the index of chrono- and inotropic reserves, which is an indication for administering appro­priate therapy. In patients with hypertension combined with COPD, the degree of desaturation, stroke volume, end-diastolic parameters of the left ventricle, maximal size and volume of the left atrium, as well as remodeling of the left heart sections in the concentric direction can be considered as independent predictors of prognosis. The 6-minute walk test with desaturation can be used as an additional method of personalizing rehabilitation measures in patients with hypertension in combination with COPD.

Abstract 244: Identifying Differences in Demographics, Management, and Outcomes Between Type 1 and Type 2 NSTEMI Patients

Background: A type 2 NSTEMI (T2) is defined as ischemia secondary to another condition resulting in either an increase in myocardial oxygen demand or decrease in oxygen supply. Little is known about this population or management. This study sought to compare demographics, outcomes, and the utility of a cardiac transitional care program (BRIDGE) between type 1 (T1) and T2 patients. Methods: The BRIDGE database was queried for patients referred between 2012-2017 with a primary discharge diagnosis of NSTEMI. Patients were randomly selected and classified as either T1 or T2 NSTEMI based on a retrospective chart review using criteria proposed by Saaby et al. (2013). Demographics, discharge medications, and outcomes (BRIDGE attendance, readmission, ED visits, death) were compared between groups. Results: Of 149 NSTEMI patients, 33 (22.1%) were T2. A higher percentage of T2 were female. T2 were more likely to have anemia and had longer hospital stays. At discharge, T2 patients were less likely to be prescribed medications for secondary prevention; specifically, aspirin, antiplatelets, or nitrates. T2 patients were less likely to attend their BRIDGE appointment. Comparison of cumulative adverse events at 180 days post-discharge was suggestive of worse outcomes for T2 patients. Conclusions: Management of the T2 NSTEMI patient depends on the underlying condition. This poses a challenge for developing universal standards. A larger sample is needed to identify standards that may be appropriate for all T2 NSTEMI patients and to identify T2 NSTEMI subsets that may share similar management strategies.

AORTIC STIFFNESS IS ASSOCIATED WITH REDUCED ADENOSINE-INDUCED HYPEREMIC MYOCARDIAL BLOOD FLOW FOLLOWING ST ELEVATION MYOCARDIAL INFARCTION

Large artery stiffness has been associated with both a reduction in myocardial perfusion and an increase in myocardial oxygen demand, so called the ‘aortocoronary relationship’. The impact of increased arterial stiffness on blood flow within ‘infarct’ and ‘non-infarct’ myocardium

Diastolic stress testing: similarities and differences between isometric handgrip and cycle echocardiography.

Cycle echocardiography (CE) is recommended for noninvasive diagnosis of diastolic dysfunction but can be limited by respiratory and movement artifact. Isometric handgrip echocardiography (IHE) is also a robust diastolic discriminator, while avoiding the limitations associated with dynamic exercise. This study sought to compare these two diastolic stress testing approaches. Twelve elderly individuals were recruited from the community (age 71 ± 6 yr). Heart rate, arterial blood pressure, and left ventricular (LV) diastolic function (via echocardiography) were assessed at rest and in response to 3 min of IHE at 40% of their maximal voluntary contraction, followed by 3 min of CE at 20 W. Both IHE and CE caused a significant increase in heart rate and blood pressure, leading to similar increases in myocardial oxygen demand. Both stressors also evoked a similar rise in the ratio between early LV mitral inflow velocity to early lateral annular velocity, a surrogate measure of LV filling pressure. The underlying mechanisms leading to these changes, however, were inherently different. IHE increased mean arterial pressure, and impaired myocardial relaxation, to a greater extent than CE. In contrast, CE augmented cardiac index, and increased early mitral filling velocity, to a great extent than IHE. In conclusion, for the first time, these data highlight several important similarities and differences between IHE and CE. That IHE avoids respiratory and movement artifact, while still serving as a robust diastolic discriminator, supports IHE as a strong alternative to CE for diastolic stress testing. NEW & NOTEWORTHY This is the first study to compare the diastolic stress response between isometric handgrip exercise and conventional cycle exercise. The data suggest that isometric handgrip echocardiography is comparable to conventional cycle echocardiography, both in terms of its hemodynamic challenge and global diastolic stress response. That isometric handgrip echocardiography eliminates both respiratory and movement artifact and is low cost and incredibly portable supports its integration into routine echocardiography exams.

Hypocapnia Measured by End-Tidal Carbon Dioxide Tension During Anesthesia Is Associated With Increased 30-Day Mortality Rate

(Abstracted from J Clin Anesth, 36:123–126, 2017) The negative effects of hypocapnia are well documented, including a decrease in cerebral blood and cognitive function, an increase in airway resistance and pulmonary cellular dysfunction, vasoconstriction and an increase in myocardial oxygen demand, hypercoagulopathy, and dysrhythmias. However, there has been no study documenting an association between hypocapnia during anesthesia and postoperative mortality.

Cardiovascular Response to Recreational Hockey in Middle-Aged Men

The present study examined the hemodynamic response to recreational pick-up hockey relative to maximal exercise testing in middle-aged men. A total of 23 men with a mean age of 53 ± 7years were studied. Graded exercise testing on a cycle ergometer determined maximal oxygen consumption, blood pressure (BP), and heart rate (HR). Ambulatory BP and Holter electrocardiographic monitoring was performed during one of their weekly hockey games (mean duration= 45 ± 7.2 minutes): for "On-Ice" responses (PLAY; data recorded while standing immediately after a shift; 8.0 ± 1.4 shifts per game) and during seated recovery (BENCH), 15minutes after the game. On-Ice HRs and BPs were significantly higher than values obtained during maximal cycle exercise, respectively (HR 174 ± 8.9 vs 163 ± 11.0 beats/min) (systolic blood pressure 202 ± 20 vs 173 ± 31mm Hg; p <0.05). Both systolic and diastolic blood pressures decreased significantly throughout the duration of the game, whereas HR increased from 139 ± 20 to 155 ± 16 beats/min during the game. The myocardial oxygen demand (myocardial time tension index) increased significantly during PLAY concurrent with a decrease in estimated myocardial oxygen supply (diastolic pressure time index), with the endocardial viability ratio during PLAY demonstrating a significant decrease during the third quarter of the game (1.25 ± 0.24) versus the first quarter (1.56 ± 0.30), which remained depressed 15minutes post-game (p <0.05). In conclusion, recreational pick-up hockey in middle-aged men is an extremely vigorous interval exercise with increasing relative intensity as the game progresses. Hockey elicits peak BPs and HRs that can exceed values observed during maximal exercise testing and is characterized by progressive increases in myocardial oxygen demand and lowered supply during PLAY and BENCH time. Given the progressive and high cardiovascular demands, caution is warranted when estimating the cardiovascular demands of hockey from clinical stress testing, particularly in those whom coronary reserve may be compromised.

Anaesthetic Management of Ischemic Heart Disease Patients in Noncardiac Surgery

Perioperative myocardial infarction is one of the most important predictors of short and long term morbidity and mortality associated with noncardiac surgery. Myocardial infraction occurs whenever myocardial oxygen supply does not match myocardial oxygen demand. Intraoperative ischemia can be precipitated by increase in myocardial oxygen demand caused by tachycardia, hypertension, anaemia, stress, sympathomimatic drugs or discontinuation of beta blocker. Clinical predictors of perioperative cardiac morbidity are acute myocardial infraction or recent myocardial infraction, unstable or severe angina, decompensated heart failure, severe valvular disease, mild angina pectoris, previous myocardial infraction, diabetic mellitus etc. The preoperative history is meant to elicit the severity, progression and functional limitations imposed by ischemic heart disease. Limited exercise tolerance in the absence of significant lung disease is very good evidence of decreased cardiac reserve. The basic challenges during induction and maintenance of anaesthesia in patients with ischemic heart disease are prevent myocardial infraction by increasing myocardial O2 supply and reducing myocardial O2 demand and monitor for ischemia and to treat ischemia if it develops. There are no one best myocardial protective agents or technique. Maintenance of balance between myocardial oxygen supply and demand is more important than the specific technique or drugs selected to produce anaesthesia and muscle relaxation. Potential benefits of a regional anaesthetic include excellent pain control, a decreased incidence of deep vein thrombosis (DVT) in some patients and the opportunity to continue the block into the postoperative period. The postoperative period appears to present the highest risk for cardiac morbidity. It is during this period where 67% of the ischemic events occur. Effective pain management is essential to prevent these adverse outcomes. Successful perioperative evaluation and treatment of cardiac patients undergoing noncardiac surgery requires careful teamwork and communication between patient, anaesthesiologist and surgeon.&#x0D; Ibrahim Cardiac Med J 2014; 4(2): 56-60

Contribution of sympathetic activation to coronary vasodilatation during the cold pressor test in healthy men: effect of ageing

The sympathetic nervous system is an important regulator of coronary blood flow. The cold pressor test (CPT) is a powerful sympathoexcitatory stressor. We tested the hypotheses that: (1) CPT-induced sympathetic activation elicits coronary vasodilatation in young adults that is impaired with advancing age and (2) combined α- and β-adrenergic blockade diminishes/abolishes these age-related differences. Vascular responses of the left anterior descending artery to the CPT were determined by transthoracic Doppler echocardiography before (pre-blockade) and during (post-blockade) systemic co-administration of α- and β-adrenergic antagonists in young (n = 9; 26 ± 1 years old, mean ± SEM) and older healthy men (n = 9; 66 ± 2 years old). Coronary vascular resistance (CVR; mean arterial pressure/coronary blood velocity) was used as an index of vascular tone. CPT decreased CVR (i.e. coronary vasodilatation occurred) in young ( -33 ± 6%), but not older men ( -3 ± 4%; P < 0.05 vs. young) pre-blockade. Adrenergic blockade abolished CPT-induced coronary vasodilatation in young men ( -33 ± 6% vs. 0 ± 6%, pre-blockade vs. post-blockade, respectively; P < 0.05) such that responses post-blockade mirrored those of older men ( -3 ± 4% vs. 8 ± 9%; both P > 0.05 compared to young pre-blockade). Impaired CPT-induced coronary vasodilatation could not be explained by a reduced stimulus for vasodilatation as group and condition effects persisted when CVR responses were expressed relative to myocardial oxygen demand (rate-pressure product). These data indicate that the normal coronary vascular response to sympathetic activation in young men is pronounced vasodilatation and this effect is lost with age as the result of an adrenergic mechanism. These findings may help explain how acute sympathoexcitation may precipitate angina and coronary ischaemic events, particularly in older adults.

Possible further reduction in coronary flow velocity reserve in angina pectoris patients after oral glucose loading.

Previous studies have suggested an increase in myocardial oxygen demand as a cause of postprandial angina. The purpose of this study was to assess coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) before and after glucose ingestion in patients with known significant LAD stenosis. Fourteen patients with significant LAD stenosis and 20 subjects without LAD stenosis were enrolled. Transthoracic Doppler echocardiography was performed to measure the average peak diastolic coronary flow velocity (APDV) in the LAD at rest and during adenosine infusion. CFVR was calculated as APDV during adenosine infusion (APDVATP) divided by APDV at rest (APDVrest). APDVrest, APDVATP, and CFVR were assessed during fasting and 30, 60, and 120min after a 75-g oral glucose loading. In patients with LAD stenosis, APDVrest at 30min after glucose loading was the highest at any time point. However, significant differences were not found in the APDVATP among time points in the patients or controls. Consequently, the CFVR in the patients was the lowest at 30min after glucose loading (fasting, 1.77±0.19; 30min, 1.48±0.16; 60min, 1.69±0.17; and 120min, 1.76±0.19; p<0.01, ANOVA), as in the controls. These findings suggested that the value of CFVR in the LAD was reduced after glucose loading. Myocardial risk area supplied by a stenosed coronary artery may be exposed to myocardial ischemia more frequently during oral glucose loading than during fasting in patients with significant coronary artery stenosis.

P 20: Coronary microvascular response to a coldpressor test and cardiac autonomic neuropathy in asymptomatic type 2 diabetic patients free of coronary stenoses

The cold-pressor test (CPT) by inducing sympathetic stimulation and a subsequent rise in myocardial oxygen demand is expected to induce an increase in coronary blood flow and a dilation of normal epicardial coronary arteries. The aim of this study was in type 2 diabetic patients (T2Ds) free of coronary stenoses to analyse the influence of cardiac autonomic neuropathy (CAN) on the coronary response to CPT measured with a non invasive method based on trans-thoracic echography-doppler (NCT00685984). We prospectively screened 118 T2Ds, without any cardiac history and fulfilling the criteria of the French guidelines, for silent myocardial ischemia (SMI: abnormal stress myocardial scintigraphy and/or echocardiography). A coronary angiography was performed in those with SMI. The distal inter-ventricular anterior coronary velocity (CV) was measured by trans-thoracic echo-doppler before and after CPT (one hand immersed in crushed ice for 120 s) in these patients and also in 16 control subjects. CAN was assessed using three standard tests (deep-breathing, lying-to-standing and Valsalva) and considered to be present if ≥2 tests were abnormal. CV before and after CPT could be measured reliably in 35 T2Ds free of coronary stenoses and with CAN function tests being performed and in all control subjects. CAN was found in 17 T2Ds. At baseline, T2Ds had higher heart rate, rate-pressure product (DP) and CV than controls (p<0.05 to <0.0001) with slightly higher levels in those with CAN. Changes after CPT/baseline in DP were lower in T2Ds with CAN than in those without CAN (26±7 vs 52±6% increase, p=0.02; 32±5% in controls) whereas changes in CV did not differ significantly in T2Ds with or without CAN and in control subjects. CV changes during CPT, i.e. related to microcirculation, correlated with DP changes in controls (r=0.45, p<0.06) and in T2Ds without CAN (r=0.65, p<0.01) but did not in those with CAN. T2Ds without evidence of coronary artery disease but with impaired vagal cardiac tests exhibit at baseline some signs of relative increase in sympathetic activity. They have a lower increase in DP after CPT which is consistent with a lower sympathetic reactivity but this increase in myocardial oxygen demand resulting from sympathetic stimulation is sufficient to increase coronary blood flow.

Coronary artery disease management with ivabradine in clinical practice

The presence of limiting angina can have a profound impact on the quality of life of patients with stable CAD, and may affect prognosis. Limiting angina symptoms are independently predictive of adverse outcomes. The aims of treating angina are to minimize or abolish symptoms and/or ischemia and to improve prognosis. Elevated HR plays an important role in the development and progression of coronary atherosclerosis, triggering ischemic events through an increase in myocardial oxygen demand and a reduction in diastolic perfusion. Reducing the HR can reduce the symptoms as well as improve the prognosis as shown in Beautiful trial. Ivabradine, a specific inhibitor of the If current in the sinoatrial node, resulting in heart rate reduction, is currently indicated for the treatment of chronic stable angina in CAD patients with a contraindication or intolerance to beta-blockers or in combination with beta-blockers in patients inadequately controlled and whose HR is above 60 bpm. In patients with a contraindication to beta blockers, ivabradine remains a preferred option as it has a well-documented anti-ischemic and antianginal efficacy through HR slowing at least comparable to that of beta-blockers, along with an excellent safety and tolerability. Therefore, ivabradine represents an important addition to the current options of different anti-ischemic agents that are available, with an impact in symptom relief as well as patient outcome.

The Role of Carvedilol in the Treatment of Dilated and Anthracyclines-Induced Cardiomyopathy

Although chronic sympathetic activation provides inotropic and chronotropic support to the failing heart, such activation may also have deleterious effects, including the direct cardiotoxic effects of catecholamines, activation of the renin-angiotensin-aldosterone system and an increase in myocardial oxygen demand. These observations indicate that β-blockade might be beneficial in the treatment of heart failure resulting from dilated cardiomyopathy or ischaemic heart disease. Carvedilol is a non-selective β-blocker acting on β1-, β2-, and α1-adrenoceptors. It possesses potent anti-oxidant and anti-apoptotic properties, along with neuroprotective, vasculoprotective, cardioprotective effects, and it has reduced overall mortality in patients with heart failure in controlled clinical trials. Its role in treating cardiomyopathy requires focus. The fact that anthracyclines are cardiotoxic seriously narrows their therapeutic index in cancer therapy. The cardiotoxic risk increases with the cumulative dose and may lead to congestive heart failure and dilated cardiomyopathy in adults and in children. This review focuses on recent research regarding the beneficial effects of carvedilol in the treatment of dilated cardiomyopathy and to revisit the available evidence on the cardioprotection of carvedilol when associated with anthracycline and to explain the mechanisms underlying the benefits of their co-administration.