Association between subjective risk perception and objective risk estimation in patients with atrial fibrillation: a cross-sectional study.

OBJECTIVE: Oral anticoagulation (OAC) is state-of-the-art therapy for atrial fibrillation (AF), the most common arrhythmia worldwide. However, little is known about the perception of patients with AF and how it correlates with risk scores used by their physicians. Therefore, we correlated patients' estimates of their own stroke and bleeding risk with the objectively predicted individual risk using CHA2DS2-VASc and HAS-BLED scores. DESIGN: Cross-sectional prevalence study using convenience sampling and telephone follow-up. SETTINGS: Eight hospital departments and one general practitioner in Austria. Patients' perception of stroke and bleeding risk was opposed to commonly used risk scoring. PARTICIPANTS: Patients with newly diagnosed AF and indication for anticoagulation. MAIN OUTCOME MEASURES: Comparison of subjective risk perception with CHA2DS2-VASc and HAS-BLED scores showing possible discrepancies between subjective and objective risk estimation. Patients' judgement of their own knowledge on AF and education were also correlated with accuracy of subjective risk appraisal. RESULTS: Ninety-one patients (age 73±11 years, 45% female) were included in this study. Subjective stroke and bleeding risk estimation did not correlate with risk scores (ρ=0.08 and ρ=0.17). The majority of patients (57%) underestimated the individual stroke risk. Patients feared stroke more than bleeding (67% vs 10%). There was no relationship between accurate perception of stroke and bleeding risks and education level. However, we found a correlation between the patients' judgement of their own knowledge of AF and correct assessment of individual stroke risk (ρ=0.24, p=0.02). During follow-up, patients experienced the following events: death (n=5), stroke (n=2), bleeding (n=1). OAC discontinuation rate despite indication was 3%. CONCLUSIONS: In this cross-sectional analysis of OAC-naive patients with AF, we found major differences between patients' perceptions and physicians' assessments of risks and benefits of OAC. To ensure shared decision-making and informed consent, more attention should be given to evidence-based and useful communication strategies. TRIAL REGISTRATION NUMBER: NCT03061123.

Expert position paper on prolonged dual antiplatelet therapy in secondary prevention following myocardial infarction.

The protective effect of dual antiplatelet therapy (DAPT) following acute coronary syndrome is undisputed, but its duration is subject of debate. Several studies show that prolonged therapy provides a clinical benefit in patients following acute coronary syndrome. The aim of this position paper authored by Austrian experts is to outline the current evidence and provide an overview of recent studies. It is also intended to serve as a practical guide to identify those patients who may benefit from prolonged DAPT.

Association of cardiorespiratory fitness and morphological brain changes in the elderly: results of the Austrian Stroke Prevention Study.

BACKGROUND: Physical activity and cardiorespiratory fitness relate to better cognitive performance. Little is known about the effects of fitness on structural brain abnormalities in the elderly. OBJECTIVE: Assess the association between maximal oxygen consumption (VO(2)max), white matter lesion (WML) volume and brain parenchymal fraction (BPF) in a large cohort of community-dwelling elderly individuals. METHODS: The study population consisted of 715 participants of the Austrian Stroke Prevention Study who underwent brain MRI with semi-automated measurement of WML volume (cm(3)) and automated assessment of BPF (%) by the use of SIENAX. A maximal exercise stress test was done on a bicycle ergometer. VO(2)max was calculated based on maximum and resting heart rate. RESULTS: After adjustment for possible confounders, VO(2)max was independently associated with WML volume (ß = -0.10; p = 0.02); no significant relationship existed with silent cerebral infarcts and BPF. Associations between VO(2)max and WML load were only significant in men, but not in women. CONCLUSION: Our findings may have important preventive implications because WMLs are known to be a major determinant of cognitive decline and disability in old age.

Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

CONTEXT: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. OBJECTIVE: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. DESIGN, SETTING, AND PARTICIPANTS: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. RESULTS: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). CONCLUSIONS: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.

ROC analysis of subcutaneous adipose tissue topography (SAT-Top) in female coronary heart disease patients and healthy controls.

The aim of this study was to investigate whether subcutaneous adipose tissue topography (SAT-Top) is different in female CHD patients (n=26) and healthy controls (n=36) matched to age, body size, weight, and BMI. The thicknesses of SAT layers were measured by LIPOMETER at 15 specified body sites. To calculate the power of the different body sites to discriminate between CHD women and healthy controls, receiver operating characteristic (ROC) curve analysis was performed. For each parameter, sensitivity and specificity were calculated at different cutoff points. CHD women showed a significant decrease to 78.36% (p=0.012) at body site 11-front thigh, 73.10% (p=0.012) at 12-lateral thigh, 72.20% (p=0.009) at 13-rear thigh, 66.43% (p<0.001) at 14-inner thigh, and 49.19% (p<0.001) at 15-calf. The best discriminators analysed by ROC curves between female CHD patients and healthy controls turned out to be calf and inner thigh (optimal cut off values: calf: 3.85 mm and inner thigh: 11.15 mm). Stepwise discriminant analysis identified the body sites calf, lateral chest, and inner thigh as significant. In conclusion, information was obtained on the extent to which SAT thickness at each measured body site is able to discriminate between the two subject groups. The good discrimination results obtained for the present dataset are encouraging enough to recommend applying LIPOMETER SAT-Top measurements in further studies to investigate individual risks for CHD.

N-terminal pro-brain natriuretic peptide identifies patients at high risk for adverse cardiac outcome after vascular surgery.

BACKGROUND: Preoperative N-terminal pro-BNP (NT-proBNP) is independently associated with adverse cardiac outcome but does not anticipate the dynamic consequences of anesthesia and surgery. The authors hypothesized that a single postoperative NT-proBNP level provides additional prognostic information for in-hospital and late cardiac events. METHODS: Two hundred eighteen patients scheduled to undergo vascular surgery were enrolled and followed up for 24-30 months. Logistic regression and Cox proportional hazards model were performed to evaluate predictors of in-hospital and long-term cardiac outcome. The optimal discriminatory level of preoperative and postoperative NT-proBNP was determined by receiver operating characteristic analysis. RESULTS: During a median follow-up of 826 days, 44 patients (20%) experienced 51 cardiac events. Perioperatively, median NT-proBNP increased from 215 to 557 pg/ml (interquartile range, 83/457 to 221/1178 pg/ml; P<0.001). The optimum discriminate threshold for preoperative and postoperative NT-proBNP was 280 pg/ml (95% confidence interval, 123-400) and 860 pg/ml (95% confidence interval, 556-1,054), respectively. Adjusted for age, previous myocardial infarction, preoperative fibrinogen, creatinine, high-sensitivity C-reactive protein, type, duration, and surgical complications, only postoperative NT-proBNP remained significantly associated with in-hospital (adjusted hazard ratio, 19.8; 95% confidence interval, 3.4-115) and long-term cardiac outcome (adjusted hazard ratio, 4.88; 95% confidence interval, 2.43-9.81). CONCLUSION: A single postoperative NT-proBNP determination provides important additional prognostic information to preoperative levels and may support therapeutic decisions to prevent subsequent structural myocardial damage.

C-reactive protein, carotid atherosclerosis, and cerebral small-vessel disease: results of the Austrian Stroke Prevention Study.

BACKGROUND AND PURPOSE: C-reactive protein (CRP) is an inflammatory marker known to be a risk factor for stroke. We examined the associations between CRP, carotid atherosclerosis, white matter lesions, and lacunes as manifestations of cerebral large- and small-vessel disease. METHODS: In the community-based Austrian Stroke Prevention Study, CRP concentrations were measured by a highly sensitive assay in 700 participants at baseline. All underwent carotid duplex scanning, and a subset of 505 subjects underwent brain magnetic resonance imaging. Imaging was repeated after 3 and 6 years. We graded carotid atherosclerosis in both common and internal carotid arteries on a 5-point scale and calculated the sum of scores as an index of the severity of carotid atherosclerosis. The volume of white matter lesions and the number of lacunes were considered small vessel disease-related brain abnormalities. RESULTS: After adjustment for vascular risk factors, the severity and progression of extracranial carotid atherosclerosis increased with increasing quintiles of CRP. Only study participants in the fourth and fifth quintile (>2.50 mg/L) had significantly more baseline atherosclerosis and greater progression when we used the first quintile (<0.80 mg/L) as a reference. No interactions were seen between CRP quintiles and vascular risk factors for carotid atherosclerosis. The associations between severity and progression of small vessel disease-related brain abnormalities and CRP were nonsignificant. CONCLUSIONS: We found evidence for differential effects of CRP in different beds of the arterial brain supply. CRP was a marker for active carotid atherosclerosis but not for small vessel disease-related brain lesions.

Continuous haemodynamic monitoring during exercise in patients with pulmonary hypertension.

BACKGROUND: Right heart haemodynamic parameters can be recorded continuously with the help of an implanted haemodynamic monitor. Aim of the study was to assess the haemodynamic response with and without inhalation of iloprost during cardiopulmonary exercise testing (CPET) in patients with pulmonary hypertension. MATERIALS AND METHODS: Five female patients with documented pulmonary hypertension (mean +/- S.D. age 47 +/- 16 years, 4 arterial, 1 venous) previously implanted with a haemodynamic monitor underwent an incremental exercise test on 2 separate days. The tests were performed before and immediately after inhalation of a single dose of iloprost (17 microg). Parameters recorded by the device were right ventricular (RV)-afterload (RV systolic pressure, RVSP), RV-preload (RV diastolic pressure, RVDP), estimated pulmonary artery diastolic pressure (ePAD), heart rate (HR) and maximum positive rate of RV pressure development (RVdP/dt) (reflecting the dynamic and inotropic state of the RV). RESULTS: After inhalation of iloprost, RV systolic pressure was always reduced at rest. It was followed by an increase with higher workloads without any difference at VO(2peak). The time course of RV systolic pressure was not linear with a flattening at higher workload during the test. This behaviour was found irrespective of iloprost treatment. The remaining determinants of RV performance showed no relevant differences and a linear behaviour during the exercise test. CONCLUSIONS: Inhalation of aerosolised iloprost resulted in a reduction in right ventricular pressure at rest but not at maximal workload. The implantable haemodynamic monitor (IHM) may be useful for the evaluation of RV haemodynamics during exercise and in assessing treatment efficacy.

Myocardial blood flow in patients with dilated cardiomyopathy: quantitative assessment with velocity-encoded cine magnetic resonance imaging of the coronary sinus.

PURPOSE: To quantify global myocardial perfusion using magnetic resonance imaging (MRI) in patients with heart failure due to idiopathic dilated cardiomyopathy (IDC) and to compare myocardial perfusion and microvascular reactivity with healthy subjects. MATERIALS AND METHODS: A total of 19 subjects (healthy volunteers (N = 12) and IDC patients (N = 7)) were studied using cine MRI to measure left ventricular (LV) mass and a velocity-encoded cine MRI technique to measure coronary sinus flow at rest and after dipyridamole-induced hyperemia. Absolute values of total myocardial blood flow (MBF) were calculated from coronary sinus flow and LV mass. RESULTS: At baseline, MBF was not significantly different in patients with IDC (0.48 +/- 0.07 mL/minute/g) and healthy subjects (0.55 +/- 0.19 mL/minute/g, P= 0.41). After dipyridamole administration, MBF in IDC patients increased to a level significantly less than that in normal volunteers (1.05 +/- 0.35 mL/minute/g vs. 1.99 +/- 1.05 mL/minute/g, P < 0.05). Consequently, MBF reserve was impaired in patients with IDC (2.19 +/- 0.77) compared to that in healthy subjects (3.51 +/- 1.29, P < 0.05). A moderate correlation was found between MBF reserve and LV ejection fraction (r = 0.48, P < 0.05). CONCLUSION: MBF reserve is reduced in patients with IDC, indicating that coronary microcirculatory flow is impaired. This integrated MRI approach allows quantitative measurement of global MBF in humans and may have the potential to study the effects of pharmacological interventions on myocardial perfusion.

Clinical applications of cardiovascular magnetic resonance.

The clinical role of magnetic resonance in diseases of the heart and great vessels is rapidly evolving. Cardiovascular magnetic resonance (CMR) has become an established non-invasive imaging modality for the assessment of various cardiac disorders, such as congenital heart disease, cardiac masses, cardiomyopathies, aortic and pericardial diseases. Moreover, due to its accuracy and reproducibility, CMR is currently considered the gold standard for quantification of ventricular volumes, function, and mass. Thus, this technique is ideally suited to assess the efficacy of therapeutic interventions on ventricular hypertrophy and remodelling, which may allow a reduction in sample size to show clinically relevant effects. Comprehensive functional assessment is possible by CMR due to its capability to measure flow velocity and flow volume, which is a basic requirement to quantify lesion severity in valvular heart disease. Within the past years, major technical advances have considerably improved acquisition speed and image quality making CMR a useful tool for the evaluation of patients with ischaemic heart disease. Although the clinical robustness of coronary magnetic resonance angiography still needs improvement, CMR currently provides valuable information to detect reversible ischemia, myocardial infarction, and residual viability. In this review we will present in detail the well-established indications of CMR accompanied by an outlook on new applications that are likely to enter the clinical arena in the near future.

Austrian survey of treating heart failure--AUSTRIA.

BACKGROUND: Treatment of chronic heart failure is based on the results of large clinical trials, which form the basis of treatment guidelines, such as those from the European Society of Cardiology (ESC). The aim of this study was to record treatment-modalities and the implementation of guidelines of chronic heart failure in clinical practice in Austria. METHODS: Overall 96 general physicians, specialists for internal medicine in private practice or in hospital outpatient departments participated in the survey. Physicians were asked to prospectively document 30 consecutive patients with chronic heart failure. RESULTS: 1880 patients were documented. The majority of patients were treated by general physicians (57%). Coronary artery disease was the most frequent aetiology for heart failure (47%). The most frequently used drugs were blockers of the renin-angiotensin-system (RAS-blocker including ACE-inhibitors and angiotensin-receptor-blockers, 78%), diuretics (76%) and beta-blockers (49%). Other drugs like digitalis and spironolactone were used infrequently. Average doses of ACE-inhibitors were approximately 90% of those recommended by the ESC, average doses of beta-blockers were approximately 50% of those recommended. Treatment among the three classes of physicians differed with respect to RAS-blockers and beta-blockers, which were used infrequently by general practitioners. Both groups of drugs were given more frequently to younger patients (<70 years) while digitalis was given more often to elderly patients. CONCLUSIONS: Results from this survey suggest that Austrian physicians treating patients with heart failure use the appropriate drugs in dosages that are suggested by recently published guidelines (ACE-inhibitors and beta-blockers). However, dosages of spironolactone clearly differed from current recommendations.

Comparison of late enhancement cardiovascular magnetic resonance and thallium SPECT in patients with coronary disease and left ventricular dysfunction.

PURPOSE: Late enhancement magnetic resonance imaging (MRI) was compared with thallium-201 rest-redistribution single photon emission computed tomography (SPECT) in patients with reduced left ventricular (LV) function and prior myocardial infarction (MI). BACKGROUND: Hyperenhancement on contrast cardiac MRI using gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) has been reported to identify nonviable myocardium. Comparisons of MRI and thallium-201 SPECT have recently been reported. This study focuses on the comparison of these modalities specifically in patients with ischemic heart failure, where viability determination is most clinically relevant. METHODS: Fifteen patients with LV dysfunction and prior MI [mean ejection fraction (EF) 35 +/- 11%] underwent thallium-201 rest-redistribution scintigraphy and contrast MRI on separate days. Each short axis slice was divided into six 60-degree segments, and correlations between MRI and scintigraphy were made on viability detection for each segment. For SPECT, the mean uptake score was calculated from the average of all percent relative activity values throughout each segment. Areas with < 50% of maximal thallium uptake were considered nonviable. On MRI, regions with increased signal intensity after an injection of 0.1 mmol/kg Gd-DPTA were considered nonviable. RESULTS: A total of 558 segments were analyzed. Overall, there was a strong inverse relationship between the area of hyperenhancement on MRI and diminished thallium-201 uptake on SPECT (r = -0.51, P < 0.001). There was a significant correlation between the imaging methods for each individual segment, except for the inferior-septal segment (r = -0.38, P < 0.08). CONCLUSIONS: In patients with LV dysfunction and prior MI, our data suggest MRI hyperenhancement significantly correlates with myocardial nonviability by thallium-201 SPECT. Correlations were weaker in the inferior-septal region, which may be due to SPECT attenuation artifact.

Continuous hemodynamic monitoring in pulmonary hypertensive patients treated with inhaled iloprost.

BACKGROUND: Aerosolized iloprost is used as an alternative to IV prostacyclin in patients with pulmonary hypertension. The desired outcome of this treatment is a reduction of pulmonary pressure, which can be measured by right-heart catheterization or Doppler echocardiography. However, both techniques provide only snapshots of the hemodynamic state. PATIENTS AND METHODS: The aim of our study was to test the usability of an implantable hemodynamic monitor (IHM) [the Chronicle, model 9520; Medtronic Inc; Minneapolis, MN] in patients with pulmonary hypertension. For this purpose, the device was implanted into five patients (mean [+/- SEM] age, 45 +/- 16 years; all women) with pulmonary hypertension who had received long-term treatment with aerosolized iloprost (100 micro g/d). Repeated short-term tests including two standard inhalations of iloprost as well as repeated long-term tests lasting 20 to 26 h, including nighttime, without inhalation were performed on an outpatient basis. RESULTS: The device provided information that was reproducible and individual for each patient during the entire study period. During short-term tests, pulmonary artery pressure was reduced from a mean (of all patients) of 68 +/- 13 to 49 +/- 11 mm Hg, with a mean total effective treatment time of 49 +/- 8 min. Thereafter, pulmonary pressure returned to preinhalation levels before the next inhalation. Long-term tests showed similar results. During a total recorded time of 15,876 min, the vasodilator effect lasted 2,140 min, corresponding to 13% of the whole time span. CONCLUSION: Our study provided new insights into the short-term and long-term effects of treatment with inhaled iloprost in patients with pulmonary hypertension. While there were no signs of tachyphylaxis, the improvement of central hemodynamics was much shorter than expected. Continuous hemodynamic monitoring with the IHM demonstrated the need to improve the treatment modalities of aerosolized iloprost in patients with pulmonary hypertension.

Chronic heart failure: global left ventricular perfusion and coronary flow reserve with velocity-encoded cine MR imaging: initial results.

PURPOSE: To quantify and compare global left ventricular (LV) perfusion and coronary flow reserve (CFR) in patients with chronic heart failure and in healthy volunteers by measuring coronary sinus flow with velocity-encoded cine (VEC) magnetic resonance (MR) imaging. MATERIALS AND METHODS: MR measurements were performed in 10 consecutive patients with chronic heart failure due to coronary artery disease and in 10 volunteers. Global LV perfusion was quantified by measuring coronary sinus flow in an oblique imaging plane perpendicular to the coronary sinus with non-breath-hold VEC MR imaging. LV mass was measured by means of cine imaging that encompassed the heart. LV perfusion was calculated from coronary sinus flow and mass. CFR was measured from LV perfusion at rest and that after infusion of dipyridamole. Analysis of covariance was used to determine differences between groups. Differences within groups were analyzed by means of the Student t test for paired data. Regression analysis was used to determine correlation between CFR and LV ejection fraction. RESULTS: At rest, LV perfusion was not significantly different in patients with chronic heart failure (0.46 mL/min/g +/- 0.19) and volunteers (0.52 mL/min/g +/- 0.21, P =.54). After administration of dipyridamole, LV perfusion was less than half in patients with chronic heart failure compared with that in volunteers (1.07 mL/min/g +/- 0.64 vs 2.19 mL/min/g +/- 0.98) (P =.03). CFR was severely reduced in patients with chronic heart failure compared with that in volunteers (2.3 +/- 0.9 vs 4.2 +/- 1.5, P =.01). A moderate but significant correlation was found between CFR and LV ejection fraction (r = 0.54, P =.02) CONCLUSION: Combined cine and VEC MR imaging revealed that patients with chronic heart failure have normal LV perfusion at rest but severely depressed LV perfusion after vasodilation. Impaired CFR may contribute to progressive decline in LV function in patients with chronic heart failure.

The potential of contrast-enhanced magnetic resonance imaging for predicting left ventricular remodeling.

PURPOSE: To determine whether the myocardial injury size on day 2 measured after gadolinium (Gd)-mesoporphyrin and Gd-diethylenetriamine-pentaacetic acid (DTPA) administration can be used for predicting left ventricular (LV) remodeling 8 weeks later, and to monitor the structural and functional changes in the infarct, peri-infarct rim, and remote myocardium in reperfused infarction using contrast-enhanced and functional magnetic resonance imaging (MRI) MATERIALS AND METHODS: Myocardial infarction (MI) was induced in 27 rats by 1 hour of coronary occlusion/reperfusion. Rats were imaged 2 days and 8 weeks after MI using MRI to determine LV function and size of myocardial injury. All animals received 0.05 mmol/kg Gd-mesoporphyrin 12 hours before the first MRI. A subgroup of 13 rats received 0.3 mmol/kg Gd-DTPA in addition to Gd-mesoporphyrin, and seven rats received 0.05 mmol/kg Gd-mesoporphyrin 12 hours before the second MRI for detection of healed MI. True infarct size (IS) and LV mass were measured postmortem. LV volumes, mass, function, and wall thickness were determined in both imaging sessions. RESULTS: A close correlation was found between contrast-enhanced MRI and postmortem measurements for IS (r = 0.94, P < 0.001 for Gd-mesoporphyrin; r = 0.91, P < 0.001, N = 13 for Gd-DTPA). IS measured on Gd-mesoporphyrin-enhanced images correlated well with end-systolic LV volumes (r = 0.68, P < 0.001) and ejection fraction (r = -0.75, P < 0.001) 8 weeks after MI. Similar correlation with parameters of LV remodeling were found on Gd-DTPA-enhanced MRI. Healed infarcts showed no enhancement on Gd-mesoporphyrin-enhanced MRI. CONCLUSION: Contrast-enhanced MRI can be used as a noninvasive method for determining the initial size of myocardial injury and predicting later LV remodeling. MRI demonstrates the structural and functional changes in infarct, peri-infarct rim, and remote non-infarcted myocardium. The complementary use of functional and contrast-enhanced MRI may provide reliable assessment of therapeutic interventions to reduce IS and LV remodeling.

Left ventricular remodeling after infarction: sequential MR imaging with oral nicorandil therapy in rat model.

PURPOSE: To use magnetic resonance (MR) imaging in quantification of the short- and long-term effects of therapy with orally administered nicorandil on left ventricular (LV) geometry and function independent of infarction size. MATERIALS AND METHODS: Forty-six rats were subjected to reperfused infarction and randomly divided into two groups. Group 1 rats (n = 21) were treated with nicorandil (3 mg/kg/day in drinking water) for 4 days before infarction and 8 weeks after infarction (hereafter, the nicorandil group). Group 2 rats (n = 25) received tap water for the same period and served as the control group. Mesoporphyrin- (as a necrosis-specific agent) enhanced MR imaging was used to define necrotic myocardium on day 2 after infarction in all 46 animals. Contrast material-enhanced MR images showed large but identical infarction size in 11 control and 11 nicorandil rats. Only these 22 rats underwent repeat MR imaging at 8 weeks after infarction. The following variables were measured: LV volumes, ejection fraction, mass, wall thickness, and infarction size. Student t test and analysis of variance for repeated measurements were used for statistical analysis. RESULTS: The size of the necrotic region on mesoporphyrin-enhanced MR images was 39% +/- 3 of the size of the left ventricle in the control group and 41% +/- 2 in the nicorandil group (difference not significant, unpaired Student t test). Pretreatment with nicorandil for 6 days before imaging did not reduce LV dilation or improve function compared with those in control animals with identical infarction size. Eight weeks after infarction, control animals showed deterioration in LV function, wall thinning, and gradient in regional dysfunction (analysis of variance test). Nicorandil produced significant salutary effects on LV ejection fraction (37% +/- 3 in the nicorandil group vs 24% +/- 3 in the control group), end-diastolic volume (0.53 mL +/- 0.03 vs 0.65 mL +/- 0.04), end-systolic volume (0.36 mL +/- 0.03 vs 0.49 mL +/- 0.05), LV wall thickening in remote noninfarcted myocardium (28% +/- 2 vs 19% +/- 1), and a rim of infarction (16% +/- 2 vs 8% +/- 1) (P <.05 for all parameters). The increase in LV mass was reduced in the nicorandil group (0.73 g +/- 0.03) compared with that in the control group (0.89 g +/- 0.04) (P <.05). CONCLUSION: In animals studied longitudinally, MR imaging demonstrated the deleterious changes in LV geometry and function in the period after infarction and the salutary effects of medical therapy.

Noninvasive assessment of the effects of nicorandil on left ventricular volumes and function in reperfused myocardial infarction.

OBJECTIVE: Nicorandil, a K-ATP channel opener with a nitrate-like effect, is a potent vasodilator and has favorable hemodynamic effects in heart failure patients. While its cardio-protective properties in the setting of acute ischemia are well known, the long-term effects of oral nicorandil therapy on post-infarction left ventricular (LV) dilatation have not been investigated. METHODS: Myocardial infarction (MI) was induced in 30 Sprague-Dawley rats by 1 h of coronary artery occlusion followed by reperfusion. After matching for infarction size, animals were randomly assigned to nicorandil treatment (3 mg/kg/day) given in tap water or no treatment (control group). Treatment was started 2 days after MI and continued for 8 weeks. Contrast-enhanced and functional magnetic resonance imaging (MRI) were used to determine infarction size, LV volumes, mass, ejection fraction, and regional wall thickness. RESULTS: Nicorandil significantly decreased end-systolic volumes (0.33+/-0.02 ml; P<0.05) and improved LV ejection fraction (37+/-2%; P<0.01) compared to control rats (0.43+/-0.04 ml and 28+/-2%, respectively) 8 weeks after MI. During the study period, the increase in LV mass (DeltaLVM) was significantly greater in control (0.09+/-0.03 g) than in treated animals (0.02+/-0.02 g, P<0.05). Moreover, nicorandil improved systolic wall thickening of the rim of infarction (P<0.001) and remote non-infarcted regions (P<0.01). CONCLUSION: These results demonstrate that the long-term oral treatment with nicorandil started 2 days after MI attenuates left ventricular dilatation and improves cardiac function in rats with reperfused MI.