Echocardiographic Wall Motion Research Articles

Prognostic Value of Echocardiography for Left Ventricular Dysfunction After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis

Cardiac dysfunction may worsen outcomes after aneurysmal subarachnoid hemorrhage (SAH). This study quantitatively assessed the prognostic value of left ventricular dysfunction with respect to functional outcomes and mortality in patients with aneurysmal SAH. We searched MEDLINE and EMBASE databases to retrieve relevant studies evaluating echocardiographic left ventricular dysfunction following aneurysmal SAH. Fourteen relevant observational studies evaluating 2234 patients were finally included in this study. Echocardiographic regional wall motion abnormalities (RWMA) and neurogenic cardiomyopathy (NCM) of the left ventricle occurring after SAH were significantly related to an increase of in-hospital mortality (in 8 studies for RWMA, odds ratio [OR] 2.37; 95% confidence interval [CI] 1.74-3.25 and in 5 studies for NCM, OR 2.82; 95% CI 1.2-6.6). Decreased ejection fraction on echocardiography was not associated with the increase of in-hospital mortality (in 4 studies, OR 1.76; 95% CI 0.86-3.61). The heterogeneities of decreased ejection fraction and NCM were significantly resolved by analyzing only the studies based on echocardiogram measurements obtained within 72 hours after admission. The present meta-analysis suggests that the identification of echocardiographic left ventricular dysfunction identified by RWMA and NCM after SAH could provide better prognostic information for in-hospital mortality.

Cornell product in an electrocardiogram is related to reduced LV regional wall motion.

Electrocardiographic left ventricular hypertrophy (LVH) diagnosed by Cornell product and the Sokolow-Lyon voltage are associated with anatomical LVH; therefore, we investigated whether Cornell product and the Sokolow-Lyon voltage were associated with echocardiographic regional wall motion (measured by 2D-strain imaging). We reviewed data on 288 consecutive hypertensive patients who underwent both echocardiography and electrocardiography. Electrocardiographic LVH was calculated as follows: Cornell voltage, S in lead V3 + R in lead aVL; Cornell product, Cornell voltage (+0.6 mV for females) × QRS duration; and Sokolow-Lyon voltage, S in lead V1 + R in lead V5. The mean age of the subjects was 64.3 ± 13.2 years; 47.9% were men, and 65.2% were taking antihypertensive medications. Both Cornell product (r = 0.392, P < 0.001) and the Sokolow-Lyon voltage (r = 0.315, P < 0.001) were significantly related to left ventricular mass index (LVMI), and the relationship between Cornell product and LVMI (beta = 0.24, P = 0.001) was independent of the Sokolow-Lyon voltage (beta = 0.25, P < 0.001). In multivariate linear regression analysis in which the two ECG-LVH were included together, Cornell product was related to global longitudinal strain (beta = 0.24, P = 0.002), even after adjusting for the Sokolow-Lyon voltage (P = 0.835). Additionally, the Cornell voltage was related to the inner/outer ratio of circumferential strain (beta = 0.17, P = 0.033) after adjusting for the Sokolow-Lyon voltage (P = 0.318). By contrast, the Sokolow-Lyon voltage was related to the relative wall thickness and E/e' on tissue Doppler imaging, even after adjusting for Cornell product. In conclusion, Cornell product and voltage were associated with longitudinal regional wall motion and with the transmurality of regional wall motion in the short axis direction.

Ischemic Evaluation in Patients Presenting with Hypertensive Emergency / Urgency and Acute Systolic Heart Failure: Is Coronary Angiography Required for all?

Patients presenting with hypertensive urgency / emergency (HUE) often have systolic heart failure(SHF). Coronary angiography is routinely done for these patients to rule out obstructive coronary artery disease (Obs-CAD). We performed a retrospective study to investigate predictors of ObsCAD in this population. Patients who underwent angiography to investigate SHF and had hospital admission(s) for HUE in the preceding 6 months were included in the study. Chart review was performed to obtain demographic, clinical and imaging / angiographic data. A risk score was formulated based on multivariable logistic regression analysis. 205 patients [age 58.9 ± 14.4 years; 62.4% male; 39.5% diabetic; median EF 25% (Inter Quartile Range: 11)] were included in the study. 33.1% patients (n = 68) had obs-CAD. Patients with obs-CAD were older, diabetic, more likely to have a history of stroke, echocardiographic regional wall motion abnormalities (RWMA) while African Americans were less likely to have obs-CAD. On multivariable analysis, only non-African American race (OR: 2.18; CI: 1.08-4.4) and RWMA (OR: 5.62; CI: 2.47-12.81) remained significant predictors of obs-CAD. A risk score (RANDS) from 0 to 9 was formulated which had a c-statistic of 0.75 with a sensitivity and specificity of 84% and 53% for predicting obsCAD respectively. Our results suggest that only a minority of patients with HUE and SHF have obs-CAD. A simple risk score may be used to stratify this population and lower risk individuals may be screened with non-invasive testing instead of invasive catheterization. These results should be validated in large registry populations.

CARDIOVASCULAR EFFECTS OF ORAL ANTIVIRAL TREATMENT FOR NON-CARDIAC HCV PATIENTS

Background: The prevalence of hepatitis C virus (HCV) in Egypt is quite high, and the combined oral direct-acting antiviral agents (DAAs) may have impressive results. Objectives: To assess the cardiovascular effects of oral antiviral treatment in non-cardiac HCV patients. Paitents and Methods: The study enrolled 100 patients with positive HCV who were enrolled for the new oral antiviral therapy in the form of Sofosbuvir and dclatsavir with or without ribavirin for 3 or 6 months. All patients on our study were subjected to follow up pre-and post-oral antiviral course, and the end point of the study was the development of a major cardiovascular event, e.g. congestive heart failure, echocardiographic evidence of left ventricular dysfunction, occurrence of significant arrhythmias, or acute coronary syndrome. The following parameters were accomplished: medical history and clinical examination, electrocardiogram, Echo-Doppler study, and laboratory investigations. Results: No significant differences were found between the patients regarding demographic criteria. None of the patients had developed any major cardiac event. No significant changes were observed regarding ST segment and T wave abnormalities, arrhythmias, or QT interval. None of patients developed echocardiographic regional wall motion abnormalities at baseline or at study end. Systolic function parameters showed minute non-significant changes over study visits. Diastolic function parameters showed non-significant changes between baseline and post oral antiviral course visit. Conclusion: The DAAs used in combination regimen didn’t significantly affect the cardiovascular system.

Impact of echocardiographic wall motion abnormality and cardiac biomarker elevation on outcome after subarachnoid hemorrhage: a meta-analysis.

Cardiac abnormalities (echocardiographic wall motion abnormality (WMA), biomarker elevation of cardiac troponin (cTn), B-type natriuretic peptide (BNP), or N-terminal prohormone of B-type natriuretic peptide (NT-proBNP)) frequently occur after subarachnoid hemorrhage (SAH). The clinical significance of cardiac abnormalities after SAH remains controversial. This meta-analysis was performed to assess the association between cardiac abnormalities and patient outcomes, including delayed cerebral ischemia (DCI), poor outcome, and death in SAH patients. PubMed and Embase were searched for observational studies reporting an association between cardiac abnormalities and outcome after SAH that were published before 31 December 2017. We extracted data regarding patient characteristics, cardiac abnormalities, and outcome measurements (DCI, poor outcome, or death). Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Twenty-six studies involving 3917 patients were included in our data analysis. WMA showed significant associations with higher rates of DCI (RR, 2.03; 95% CI, 0.99-4.15), poor outcome (RR, 1.45; 95% CI, 1.08-1.93), and death (RR, 2.54; 95% CI, 1.59-4.05). cTn elevation was associated with an increased risk of DCI (RR, 1.48; 95% CI, 1.23-1.79), poor outcome (RR, 1.85; 95% CI, 1.49-2.30), and death (RR, 2.68; 95% CI, 2.19-3.27). Elevation of BNP or NT-proBNT was significantly associated with higher rates of DCI (RR, 1.87; 95% CI, 1.16-3.02). WMA and elevation of cTn, BNP, and NT-proBNP in SAH patients are associated with an increased risk of DCI, poor outcome, and death after SAH.

Wall motion score index predicts mortality after coronary artery bypass grafting in patients with viable non-functioning myocardium

Coronary artery bypass grafting (CABG) has better survival than medical treatment in patients with left ventricular (LV) dysfunction. Assessment of myocardial viability is crucial to predict survival benefit after CABG. Our recent work determined higher prognostic value of echocardiographic wall motion score index (WMSI) than left ventricular ejection fraction (LVEF) in patients underwent CABG with viable myocardium and LVEF <50%. Thus, it is important to determine the extent of nonviable as well as viable myocardium in patients with low LVEF. Also, in the absence of high modality imaging studies like cardiac magnetic resonance (CMR) and to avoid the radiation hazards of radionuclide studies, assessment of WMSI in addition to LVEF can give accurate data of the magnitude of myocardial damage and can predict survival after CABG in patients with systolic LV dysfunction.

The Incidence of Perioperative Cardiac Events after Orthopedic Surgery: A Single Institutional Experience of Cases Performed over One Year

BackgroundOrthopedic patients with ischemic heart disease are at risk for postoperative cardiac complications.Questions/PurposesUsing information from two medical information retrieval systems which insured the capture of all events for the period of study, our goals were to determine the incidence of myocardial injury in at-risk patients after orthopedic surgery and to delineate the type and incidence of cardiac complications in this population.MethodsFor one year, at an orthopedic hospital, we identified all postoperative patients with a measured cTnI level using an electronic ordering system. Preoperative cardiac risk factors and postoperative cardiac complications were identified in patients undergoing a total hip arthroplasty (THA), total knee arthroplasty (TKA), and posterior spinal fusion (PSF). A postoperative myocardial infarction was defined by a cTnI > 0.1 ng/mL, ECG changes, new echocardiographic regional wall motion abnormalities, and evaluation by a cardiologist. Categorical variables were compared among groups with a Fisher’s exact or Chi-square test. Continuous variables were compared among groups with ANOVA or the Kruskal-Wallis test. The associations of cardiac risk factors with myocardial injury are expressed as odds ratios from logistic regression models.ResultsDuring a one-year period, from 10,627 inpatient orthopedic procedures, 805 patients were identified as at risk for postoperative myocardial ischemia. A total of 20.6% (166/805) of these patients had elevated serum cTnI levels (cTnI > 0.02 ng/mL), and there were ten documented postoperative MIs (10/805; 1.2%). For the at-risk TKA, THA, or PSF patients, 19% (102/532) had elevated cTnI levels and 31% (32/102) had postoperative cardiac complications, including arrhythmias (56%), congestive heart failure (2%), and MI (1%). Adjusting for sex, age, BMI, cardiac risk factors, and medications (statins and β-blockers), PSF patients had 3.9 times the risk of myocardial injury (p = 0.003) compared to TKA patients and 4.2 times that of THA patients.ConclusionsThe incidence of postoperative myocardial ischemia after major orthopedic surgery in patients with cardiac risk factors is high (8.7%), but the incidence of documented myocardial infarctions and serious cardiac complications remains low (1.2–2%). Patients with higher postoperative cTnI releases were more likely to have cardiac complications, and some procedures (spinal fusions) placed the patients at a higher risk.

Effect of Chronic Hepatitis C Virus Treatment by Combination Therapy on Cardiovascular System.

BACKGROUNDThe prevalence of hepatitis C virus (HCV) in Egypt is quite high, and the combined oral direct-acting antiviral agents (DAAs) may have impressive results.OBJECTIVETo assess the cardiovascular effects of DAAs in patients with HCV.METHODSA total of 170 patients with HCV were divided into 2 groups: first group (100 patients) received triple combination therapy (pegylated interferon alfa, sofosbuvir, and ribavirin, whereas the second group (70 patients) received dual combination therapy (sofosbuvir and simeprevir). Group 1 patients were followed up for 1 year more than 3 visits, whereas group 2 patients were followed up for 6 months more than 2 visits; and the end point of the study was the development of a major cardiovascular event (eg, congestive heart failure, echocardiographic evidence of left ventricular dysfunction, occurrence of significant arrhythmias, or acute coronary syndrome). The following parameters were accomplished: medical history and clinical examination, electrocardiogram, echo-Doppler study, and laboratory investigations.RESULTSNo significant differences were found between the 2 study groups regarding demographic criteria. None of the both group patients had developed any major cardiac event. No significant changes were observed regarding ST-T wave abnormalities, arrhythmias, or QT interval. None of the both group patients developed echocardiographic regional wall motion abnormalities at baseline or at study end. Systolic function parameters showed minute nonsignificant changes over study visits. Diastolic function parameters showed nonsignificant changes between baseline and 6-month and 12-month visits.CONCLUSIONSThe DAAs used in combination regimen with interferon or used orally in combination do not significantly affect the cardio-vascular system.

Abstract 12654: PBI-4050 Therapy Selectively Improves Pulmonary Hypertension, Lung Remodeling and Right Ventricular Function in Heart Failure With Reduced Ejection Fraction

Introduction: There is currently no approved treatment for the most prevalent form of PH that is associated with left heart disease (Group II PH). Heart failure with reduced ejection fraction (HFrEF) causes lung remodeling characterized by myofibroblasts proliferation and fibrosis leading to a restrictive lung syndrome contributing to PH and RV dysfunction. Hypothesis: We evaluated PBI-4050, a novel first-in-class agent with anti-fibrotic and anti-proliferative actions, for the treatment of PH in a model of HFrEF. Methods: HFrEF was induced by myocardial infarction (MI) after coronary artery ligation in rats. Two weeks after surgery, sham-operated and MI groups were treated with PBI-4050 (200 mg/kg/day by gavage) or with saline for 3 weeks. Animals were analyzed according to pathological infarct size into large MI (≥35% LV) and small to medium MI (&lt; 35%). Hemodynamic evaluation was performed with microtip cathethers and lung function testing evaluated with a Flexivent respirator. Cardiac ultrasound was performed at 2 weeks and at 5 weeks. Scar size and lung fibrosis were quantified by histology. Results: Pathological infarct size correlated with echocardiographic wall motion score index (r 2 =0.73, p&lt;0.001). Large MI (≥35% LV) resulted in PH and RVH with a restrictive lung syndrome. For a similar infarct size, PBI-4050 did not affect LV function but markedly reduced PH and RVH. The compensatory increase in RV contractility was normalized by PBI-4050. PBI-4050 reduced lung remodeling evidenced by a reduction in lung weight and improved respiratory compliance. Finally, lung fibrosis was reduced by PBI-4050 with histological evidence of reduced alveolar wall cellular proliferation. Conclusions: PBI-4050 effectively reduces PH and RVH in HFrEF by reducing lung fibrosis and remodeling. This novel agent decreases the associated restrictive lung syndrome and recovers RV function without affecting LV function. PBI-4050 is a promising therapy for group II PH.

Left ventricular regional contraction abnormalities by echocardiographic speckle tracking in combined right bundle branch with left anterior fascicular block compared to left bundle branch block

BackgroundIn contrast to LBBB patients less is known about patients with RBBB+LAFB regarding LV contractile abnormalities and the potential role of CRT. This study investigated whether patients with RBBB+LAFB morphology have echocardiographic mechanical strain abnormalities between the inferior and anterior LV walls, similar to abnormalities between septal and lateral walls in LBBB. Methods and resultsTen healthy volunteers with no-BBB, 28 LBBB and 28 RBBB+LAFB heart failure patients were included in this retrospective study. Two-dimensional regional-strains were obtained by speckle-tracking. Scar was assessed by CMR. Response on echo was defined as normal, classical, borderline or other pattern. The number of classical patterns in LBBB was significantly higher than in RBBB+LAFB and no-BBB groups (p<0.001 for both). Contrary, the RBBB+LAFB group showed a significantly higher number of borderline patterns compared to other groups (LBBB: p=0.042, no-block: p=0.012). In addition, RBBB+LAFB patients had more scar than LBBB patients (9.9% vs 3.4%, p=0.041), and the average amount of scar in each wall was also higher in RBBB+LAFB (<5% in LBBB and <16% in RBBB+LAFB). ConclusionsPatients with RBBB+LAFB on ECG and clinical HF demonstrate echocardiographic wall motion abnormalities between inferior and anterior LV walls, similar to abnormalities found between septal and lateral LV walls in patients with LBBB and HF. Fewer patients with RBBB+LAFB showed a classical pattern of opposing wall motion compared to LBBB. Factors that might alter strain patterns in RBBB+LAFB, including the detailed presence or absence of LV scar and coexisting block of the central fascicle, should be assessed in future studies.

Myocarditis in patients with subarachnoid hemorrhage: A histopathologic study

Cardiac abnormalities after subarachnoid hemorrhage (SAH) such as electrocardiographic changes, echocardiographic wall motion abnormalities, and elevated troponin levels are independently associated with a poor prognosis. They are caused by catecholaminergic stress coinciding with influx of inflammatory cells into the heart. These abnormalities could be a sign of a myocarditis, potentially giving insight in pathophysiology and treatment options. These inflammatory cells are insufficiently characterized, and it is unknown whether myocarditis is associated with SAH. Myocardium of 25 patients who died of SAH and 18 controls was stained with antibodies identifying macrophages (CD68), lymphocytes (CD45), and neutrophil granulocytes (myeloperoxidase). Myocytolysis was visualized using complement staining (C3d). CD31 was used to identify putative thrombi. We used Mann-Whitney U testing for analysis.In the myocardium of SAH patients, the amount of myeloperoxidase-positive (P < .005), CD45-positive (P < .0005), and CD68-positive (P < .0005) cells was significantly higher compared to controls. Thrombi in intramyocardial arteries were found in 22 SAH patients and 1 control. Myocytolysis was found in 6 SAH patients but not in controls.Myocarditis, consisting of an influx of neutrophil granulocytes, lymphocytes, and macrophages, coinciding with myocytolysis and thrombi in intramyocardial arteries, occurs in patients with SAH but not in controls. These findings might explain the cardiac abnormalities after SAH and may have implications for treatment.

Abstract 15647: Mental Stress-Induced Reductions in Left Ventricular Ejection Fraction Predict Future Heart Failure Exacerbation

Background: Mental stress-induced myocardial ischemia (MSIMI) is common in patients with ischemic heart disease (IHD) and has been associated with an elevated risk of mortality and adverse cardiac events. Microcirculation dysfunction may have a critical mechanistic role as MSIMI has been associated with microvascular constriction but not epicardial coronary stenotic burden. This may also play a role in the etiology of heart failure and other cardiovascular (CV) events. We explored the relationship of MSIMI to heart failure exacerbations and other categories of CV events using data from the REMIT trial. Methods: Patients with stable IHD (N=310) underwent mental and exercise tress testing; 44% had mental stress induced myocardial ischemia (by echocardiographic wall motion abnormality, left ventricular ejection fraction (LVEF) reduction of &gt; 8%, and/or ischemic ST-change on ECG). Patients were followed for up to 6 years (median 4 yrs) for all-cause mortality and CV events resulting in hospitalization. Cox proportional hazard models, controlling for age, sex, and resting LVEF, were used to examine the associations of MSIMI indices with each CV category. Results: MSIMI, as a dichotomous variable, was not significantly associated with any CV category. Continuous mental stress-induced LVEF change scores were linearly associated with risk of being hospitalized for a heart failure exacerbation (HR = 2.35, 95%CI = 1.30 - 4.25,p=.005) (Table). This association did not significantly change after controlling for exercise-induced LVEF changes (HR = 2.35, 95%CI = 1.24 - 4.47,p=.009). Conclusion: In patients with stable IHD, every incremental 5% reduction in LVEF change induced by mental stress was associated with a 2.35 times greater risk of experiencing a hospitalization for heart failure exacerbation over an average 4-year period. This is independent of the risk conferred by traditional exercise testing.

Association of serum cystatin C levels with myocardial perfusion and cardiac functional recovery in patients with anterior wall ST elevation myocardial infarction treated with primary coronary intervention.

This study sought to investigate the association of baseline serum cystatin C levels with myocardial perfusion and cardiac functional recovery in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). 108 patients with a first anterior STEMI who underwent PPCI were enrolled. Serum cystatin C was measured by immunoturbidimetric method. Patients were divided into two groups according to the median cystatin C levels on admission: group 1 (≥median, n=54) and group 2 (<median, n=54). Myocardial perfusion was assessed by angiographic criteria, ST-segment resolution, and the index of microcirculatory resistance (IMR). Echocardiographic wall motion score index was analyzed on admission and at 6-month follow-up. Patients with angiographically, electrocardiographically no-reflow had significantly higher cystatin C levels on admission. Patients with an IMR ≥33.7 U also had significantly higher cystatin C levels. The WMSI showed a greater improvement in group 2 than in group 1 and there was a significant negative correlation between improvement of WMSI and the cystatin C levels. There was no significant difference in MACEs between the 2 groups. However, congestive heart failure (CHF) was observed significantly more frequent in group 1 than in group 2 (18.5 vs. 5.6%, p=0.022). Multivariate logistic regression analysis demonstrated that cystatin C levels at admission were a significant independent predictor of angiographic no-reflow and the development of CHF at 6-month follow-up. Elevated cystatin C levels at admission were independently associated with impaired myocardial perfusion, poor cardiac functional recovery and development of CHF in patients with anterior STEMI undergoing PPCI.

Inferior Q waves in apparently healthy subjects: Should we take a deep breath? An electrocardiographic, echocardiographic and cardiac magnetic resonance study

AimTo evaluate the diagnostic accuracy of electrocardiographic inferior Q waves persistence during inspiration and echocardiographic segmental wall motion abnormalities for the detection of previously unsuspected silent myocardial infarction, by using cardiac magnetic resonance as the gold standard. MethodsWe prospectively enrolled 50 apparently healthy subjects with inferior Q waves on routine electrocardiogram and high atherosclerotic risk profile. Patients underwent electrocardiogram during deep inspiration, standard transthoracic echocardiography, and cardiac magnetic resonance. ResultsInferior Q waves during deep inspiration persisted in 10 subjects (20%) and cardiac magnetic resonance was positive in 10 (20%). Between the 10 positive cardiac magnetic resonance subjects 8 showed persistence of inferior Q waves, giving a sensitivity of 80% (95%;CI 44.4–97.5%) and a specificity of 95% (95%;CI 83.1–99.4%). Segmental wall motion abnormalities were present overall in 10 subjects (20%), but only in 5 of the 10 positive cardiac magnetic resonance subjects, giving a sensitivity of 87.5% (95% CI 73.2–95.8) and specificity of 50% (95% CI 18.7–81.3). ConclusionsElectrocardiographic inferior Q waves persistence during deep inspiration is a simple test with a high accuracy for diagnosis of silent myocardial infarction. Standard echocardiography resulted less accurate.

Neurogenic Stress Cardiomyopathy After Aneurysmal Subarachnoid Hemorrhage

Neurogenic stress cardiomyopathy (NSC) is a known complication of aneurysmal subarachnoid hemorrhage (SAH). Detailed analyses of risk factors for its occurrence across large cohorts are relatively sparse. A consecutive group of 300 patients with aneurysmal SAH was reviewed for the presence of markers of myocardial injury, including electrocardiogram changes (long QT, T-wave inversion), elevated plasma troponin levels (≥0.1), and echocardiogram findings (decreased ejection fraction and wall motion abnormalities). NSC was defined as the presence of at least 1 marker of myocardial injury. Univariate and multivariate analyses were conducted to assess the correlation of NSC and individual markers of myocardial injury with age, gender, medical comorbidities, medications, current smoking status, Hunt-Hess grade, and Fisher grade. Medical comorbidities were assessed based on reported medical history or reported use of comorbidity-specific medications at the time of presentation. Across the cohort, 27% of patients had a plasma troponin elevation of at least 0.1; 13%, a prolonged QT interval; 16%, new T-wave inversions; 18%, a depressed ejection fraction (<55%); and 15%, echocardiographic wall motion abnormalities. After a multivariate analysis, significant risk factors for NSC included higher Hunt-Hess grade on presentation (odds ratio [OR] = 2.33, P = 4.52 × 10(-6)), current smoking status (OR = 2.00, P = 0.030), and older age (OR = 1.03, P = 0.048). Hypertension was protective against NSC (OR = 0.48, P = 0.031). Patient gender, hyperlipidemia, diabetes, coronary artery disease, statin use, beta blocker use, angiotensin-converting enzyme inhibitor use, aspirin use, and thicker SAH (Fisher grade 3) were not significant risk factors for NSC. Higher Hunt-Hess grade, current smoking status, lack of hypertension, and older age were the strongest predictors of NSC.

Development of an experimentally useful model of acute myocardial infarction: 2/3 nephrectomized triple nitric oxide synthases-deficient mouse

We investigated the effect of subtotal nephrectomy on the incidence of acute myocardial infarction (AMI) in mice deficient in all three nitric oxide synthases (NOSs). Two-thirds nephrectomy (NX) was performed on male triple NOSs−/− mice. The 2/3NX caused sudden cardiac death due to AMI in the triple NOSs−/− mice as early as 4months after the surgery. The 2/3NX triple NOSs−/− mice exhibited electrocardiographic ST-segment elevation, reduced heart rate variability, echocardiographic regional wall motion abnormality, and accelerated coronary arteriosclerotic lesion formation. Cardiovascular risk factors (hypertension, hypercholesterolemia, and hyperglycemia), an increased number of circulating bone marrow-derived vascular smooth muscle cell (VSMC) progenitor cells (a pro-arteriosclerotic factor), and cardiac up-regulation of stromal cell-derived factor (SDF)-1α (a chemotactic factor of the progenitor cells) were noted in the 2/3NX triple NOSs−/− mice and were associated with significant increases in plasma angiotensin II levels (a marker of renin–angiotensin system activation) and urinary 8-isoprostane levels (a marker of oxidative stress). Importantly, combined treatment with a clinical dosage of an angiotensin II type 1 receptor blocker, irbesartan, and a calcium channel antagonist, amlodipine, markedly prevented coronary arteriosclerotic lesion formation and the incidence of AMI and improved the prognosis of those mice, along with ameliorating all those pro-arteriosclerotic parameters. The 2/3NX triple NOSs−/− mouse is a new experimentally useful model of AMI. Renin–angiotensin system activation, oxidative stress, cardiovascular risk factors, and SDF-1α-induced recruitment of bone marrow-derived VSMC progenitor cells appear to be involved in the pathogenesis of AMI in this model.

The spectrum of electrocardiographic manifestations of acute myocarditis: An expanded understanding

Background and PurposeDescriptions of the significance of ST segment or QRS abnormalities in myocarditis are limited because documentation of the diagnosis has previously required myocardial biopsy. Late gadolinium enhancement (LGE) and T2 weighted imaging in the midventricular wall on cardiac magnetic resonance imaging (CMRI) has a very good positive predictive value for the diagnosis of myocarditis. We hypothesized to reexplore the diagnostic value of these electrocardiographic (ECG) changes in myocarditis by utilizing CMRI as the reference standard. MethodsData on demographics, clinical presentation, laboratory tests, echocardiograms, coronary angiograms, and computed tomography angiography of 41 consecutive patients with definite midventricular or subepicardial LGE and T2 weighted imaging on CMRI were extracted from the available clinical records. ECGs were blindly examined by two independent readers and divided based on (a) STT changes into: 1. No STT changes, 2. STT changes but no ST elevation, 3. ST elevation (STE); and (b) the presence or absence of QRS abnormalities. Associations of these ECG changes with differences in left ventricular ejection fraction, as measured from CMRI was the main aim of this study. In addition, a complete clinical profile of these patients with myocarditis as identified by CMRI was also created. Results80% of our study population were male with a mean age of 38.6±15.5 and a paucity of traditional cardiovascular risk factors (<30%). 90% presented with chest pain with more than half having dyspnea and a viral prodrome, but fever was infrequent (15%). Peak troponin-I and creatine kinase-MB levels exceeded the upper limit of normal in latest 85%, often by more than 5 times the limit. 18% had a coronary luminal narrowing of ≥50%, while 56% had echocardiographic wall motion abnormalities. The left ventricular ejection fraction averaged 54.3±10.8%. In 24.4% of patients, the ECG was entirely normal; while 39% had STE. STT changes did not detect any differences in the ejection fraction. An abnormal QRS, which was present in 29%, was associated with a lower left ventricular ejection fraction (p=0.005). ConclusionsPatients with clinical features suggestive of myocarditis and confirmatory CMRI findings, can present with a variety of ECG findings, some of which have the potential to identify those with a worse cardiac function, and potentially with a worse prognosis.

Coronary microvascular spasm triggers transient ischemic left ventricular diastolic abnormalities in patients with chest pain and angiographically normal coronary arteries

AimsImpaired coronary microvascular dilatory function can lead to exercise induced myocardial ischemia and angina pectoris even in patients without significant (>50%) obstructive coronary atherosclerosis (APWOCA). Diffuse distal vessel epicardial spasm and microvascular spasm have been also proposed as a plausible explanation for angina at rest in these patients. However, objective systematic evidence for the latter i.e. echocardiographic wall motion abnormalities during angina, is lacking at present. Coronary epicardial and microvascular spasm can be triggered in susceptible patients by the administration of intracoronary acetylcholine (Ach). We sought to assess whether Ach induced diffuse distal epicardial coronary artery spasm (≥75% diameter reduction) and coronary microvascular spasm can cause transient ischemic left ventricular dysfunction, as assessed by echocardiography. Methods50 patients (19 men aged 60.5 ± 8.9 years) with stable APWOCA were assessed for coronary spasm and myocardial ischemia with intracoronary Ach infusion, 2D transthoracic echocardiography (before and during Ach testing), continuous 12-lead ECG monitoring, and ultrasensitive cardiac troponin (US-cTn) measurement before and within 4 h after Ach testing. Results14 patients (28%) had a “negative” Ach test, 14 (28%) developed coronary microvascular spasm and 17 (34%) had diffuse distal epicardial spasm. In 5 patients (10%) the test was inconclusive. Echocardiographic variables including deceleration time, EF slope and E/A, as well as ultrasensitive-cTn concentrations were abnormal during Ach induced ischemic ECG changes. Conclusions: We have, for the first time, demonstrated that Ach induced coronary microvascular spasm is associated with echocardiographic changes and ultrasensitive-cTn elevations, indicative of myocardial ischemia.

Evidence of myocardial scarring and microvascular obstruction on cardiac magnetic resonance imaging in a series of patients presenting with myocardial infarction without obstructed coronary arteries.

Patients with acute chest pain, electrocardiographic ST-elevation and significant elevation of cardiac troponin but without obstructive coronary artery disease represent a diagnostic and therapeutic dilemma. Cardiac magnetic resonance imaging (CMR) can elucidate underlying alternative causes of troponin elevation including detection of (minor) myocardial infarction (MI) by identifying myocardial scarring as delayed enhancement. Of 77 patients, who were admitted between March 2009 and December 2012 with electrocardiographic (ECG) and biochemical evidence of acute MI without obstructive coronary artery disease, 45 patients underwent CMR that showed in 11/77 (14%) late gadolinium enhancement (LGE), compatible with myocardial scarring. We analyzed clinical, echocardiographic, and CMR data of these patients. Elevated troponin I levels were observed in all patients (median 1.3 ng/l, IQR 0.44-187) with median peak creatinine phosphokinase of 485 U/l (IQR 234-618). Echocardiographic wall motion abnormalities were detected in 8/11 (73%) patients; in 75% of these segments, ECG abnormalities were observed in corresponding leads. CMR detected LGE in the inferior (4/11), the inferolateral (5/11), the inferoseptal (2/11), the anterior (3/11), apical (3/11) and in the lateral segments (2/11). In addition, in all but two patients, these segments matched ECG abnormalities in corresponding leads. CMR identified microvascular obstruction in 4/11 (36%) patients. Patients with clinical, ECG, and biochemical signs of acute MI but unobstructed coronary arteries may have CMR-detectable myocardial scars. Information on myocardial scarring may help to make the diagnosis and draw therapeutic consequences. This case series underlines the value of contrast-enhanced CMR for myocardial tissue characterization.

Reliable exclusion of acute coronary syndrome among hospitalized patients with elevated troponin.

Elevated cardiac troponin I (cTnI) occurs in acute coronary syndrome (ACS) as well as various scenarios not associated with ACS. Simple clinical criteria can reliably exclude ACS among hospitalized patients with elevated cTnI. Records for patients hospitalized from January to April 2011 with elevated cTnI (>0.29 ng/dL) and an available echocardiogram were retrospectively reviewed. Patients with ST-segment elevation myocardial infarction were excluded. Based on available clinical data, patients were classified as having ACS or elevation of cTnI unrelated to ACS (non-ACS). Median follow-up was 365 days. Of 265 records meeting inclusion criteria, 82 (31%) had ACS and 183 (69%) had non-ACS. In multivariable analysis, odds ratios for non-ACS were 7.6 (95% confidence interval [CI]: 3.8-15.3) for peak cTnI <2 ng/dL, 6.3 (95% CI: 3.1-13.0) for absent wall-motion abnormality, and 4.4 (95% CI: 2.2-8.6) for no prior coronary artery disease history. The area under the receiver operating curve for amodel using these 3 variables was 0.86, with a 98% negative predictive value for excluding ACS. Patients who met these 3 criteria had no ACS-related deaths over 1-year follow-up. Hospitalized patients with peak Tn level<2 ng/dL, no prior history of coronary artery disease, and no new echocardiographic wall-motion abnormality appear to have a very low likelihood of ACS. Prospective validation of these results is needed to determine whether additional diagnostic testing could be safely avoided in hospitalized patients meeting these simple clinical criteria.