Prognosis of patients with secondary mitral regurgitation and reduced ejection fraction.

Objective: The impact of the severity of secondary mitral regurgitation (MR) on the risk of death and heart failure (HF) hospitalisations in patients with reduced left ventricular (LV) systolic function is poorly defined. The study sought to identify the incremental risk of secondary MR in patients with reduced LV systolic function. Methods: We studied 615 consecutive patients with LV ejection fraction ≤35% by transthoracic echocardiography at a single medical centre. Patients were divided into three groups of no MR, mild, or moderate to severe MR. The median follow-up was 2.9 years. The primary endpoint was a composite of death or HF hospitalisations. Results: Compared with patients with no MR, the risk of death or HF hospitalisations was higher for mild MR (HR 1.7, P=0.003) and moderate to severe MR (HR 2.7, P<0.001). The risk was also higher for the component endpoints of HF hospitalisations (mild MR: HR 2.3, P=0.001; moderate to severe MR: HR 3.5, P<0.001) and death (mild MR: HR 1.6, P=0.033; moderate to severe MR: HR 2.6, P<0.001). After adjustment for other covariates, MR was no longer significantly associated with death or HF hospitalisations, or death alone, but remained significantly associated with HF hospitalisations (mild MR: HR 1.7, P=0.028; moderate to severe MR: HR 2.2, P=0.002). Conclusions: In patients with reduced LV systolic function, secondary MR is associated with an increased risk of HF hospitalisations but not death.

T-wave inversion and diastolic dysfunction in patients with electrocardiographic left ventricular hypertrophy.

OBJECTIVES: The aim of this study was to investigate if T-wave inversion (TWI) in the settings of electrocardiogram (ECG)-left ventricular hypertrophy (LVH) is associated with advanced diastolic dysfunction (DD) in subjects with preserved ejection fraction (EF). BACKGROUND: Animal studies suggested that an abnormal transmural repolarization sequence from endocardium to epicardium may contribute to DD. However, little is known about abnormal repolarization sequence and DD in humans. METHODS: We studied 231 patients with ECG-diagnosed LVH and with an EF of 50% or greater (measured within 6 months of the index ECG). T-wave inversion was assessed on leads I, aVL, V(4), V(5), or V(6). Diastolic dysfunction was defined based on echocardiographic estimation of the left atrial pressure. We used multiple logistic regression to estimate the odds ratio of DD comparing patients with TWI with those without TWI. RESULTS: The average age was 65.0 ± 14.2 years, and 61% were women. The mean EF was 61.8% ± 6.6%. Patients with TWIs were more likely to have coronary artery disease (P = .013) and diabetes (P = .007). There was a 5.6-fold increased odds of DD in patients with TWI compared with those without TWI in a model adjusting for sex, age, relative wall thickness, body mass index, hypertension, coronary artery disease, diabetes, hyperlipidemia, and smoking. When comparing different echocardiographic estimates of the left atrial pressure, patients with TWI displayed higher values for septal and lateral E/e', left atrial volume index, and right ventricular/right atrial peak systolic gradient (P < .01 for each parameter). CONCLUSIONS: T-wave inversion is associated with increased odds of DD in patients with ECG-LVH with preserved systolic function. The reversal of the normal sequence of repolarization manifested on the 12-lead ECG as TWI may be a factor to DD.

Left atrial passive emptying function during dobutamine stress MR imaging is a predictor of cardiac events in patients with suspected myocardial ischemia.

OBJECTIVES: The aim of this study was to determine the prognostic value of assessing left atrial function during dobutamine stress testing. BACKGROUND: Left ventricular diastolic dysfunction precedes systolic wall motion abnormalities in the ischemic cascade. Severity of left ventricular diastolic function during cardiac stress is not characterized well by current clinical imaging protocols but may be an important prognostic factor. We hypothesized that abnormal early left atrial emptying measured during dobutamine stress cardiac magnetic resonance will reflect these diastolic changes and may be associated with cardiovascular outcomes. METHODS: We enrolled 122 consecutive patients referred for dobutamine stress cardiac magnetic resonance for suspected myocardial ischemia. Left atrial volumes were retrospectively measured by the biplane area-length method at left ventricular end-systole (VOL(max)) and before atrial contraction (VOL(bac)). Left atrial passive emptying fraction defined by (VOL(max) - VOL(bac)) × 100%/VOL(max) and the absolute percent increase in left atrial passive emptying fraction during dobutamine stress (ΔLAPEF) were quantified. RESULTS: Twenty-nine major adverse cardiac events (MACE) occurred during follow-up (median 23 months). By Kaplan-Meier analysis, patients with ΔLAPEF <10.8 (median) experienced higher incidence of MACE than did patients with a ΔLAPEF >10.8 (p = 0.004). By univariable analysis, ΔLAPEF was strongly associated with MACE (unadjusted hazard ratio for every 10% decrease = 1.56, p < 0.005). By multivariable analysis, every 10% decrease in ΔLAPEF carried a 57% increase in MACE, after adjustment to presence of myocardial ischemia and infarction. CONCLUSIONS: Reduced augmentation of left atrial passive emptying fraction during dobutamine stress demonstrated strong association with MACE. We speculate that reduced left atrial passive emptying reserve during inotropic stress may represent underlying diastolic dysfunction and warrants further investigation.

Incremental prognostic value of gated Rb-82 positron emission tomography myocardial perfusion imaging over clinical variables and rest LVEF.

OBJECTIVES: This investigation sought to study the incremental value of gated rubidium (Rb)-82 positron emission tomography (PET) myocardial perfusion imaging (MPI) over clinical variables for predicting survival and future cardiac events. BACKGROUND: The prognostic value of Rb-82 PET-MPI and left ventricular ejection fraction (LVEF) reserve (stress minus rest LVEF) is not well defined. METHODS: 1,432 consecutive patients undergoing gated rest/vasodilator stress rubidium-82 PET were followed up for at least 1 year. Of these, rest and peak stress LVEF and LVEF reserve were available in 985 patients. Cardiac events (CE) including cardiac death or nonfatal myocardial infarction and all-cause death were assessed. RESULTS: Over a mean follow-up of 1.7 +/- 0.7 years, 83 (5.8%) CE and 140 (9.7%) all-cause death were observed. There was an increase in risk for both end points with an increasing percentage of abnormal and ischemic myocardium. With normal, mild, moderate, or severely ischemic scans, the observed annualized rates of CE were 0.7%, 5.5%, 5%, and 11% and of all-cause death were 3.3%, 7.2%, 6.9%, and 12.5%, respectively. In 985 patients with peak stress gated data, the observed annualized rates of CE (2.1% vs. 5.3%, p < 0.001) and all-cause death (4.3% vs. 9.2%, p < 0.001) were higher in patients with an LVEF reserve <0% compared with those with an LVEF reserve >or=0%. On Cox proportional hazards analysis, after consideration of clinical, historical, and rest LVEF information, stress PET results and LVEF reserve yielded incremental prognostic value with respect to both CE and all-cause death. CONCLUSIONS: Vasodilator stress Rb-82 PET-MPI provides incremental prognostic value to historical/clinical variables and rest LVEF to predict survival free of CE and all-cause death. An increasing percentage of ischemia on PET-MPI is associated with an increase in the risk of CE and all-cause death. Left ventricular ejection fraction reserve provides significant independent and incremental value to Rb-82 MPI for predicting the risk of future adverse events.

Quantitative relationship between coronary calcium content and coronary flow reserve as assessed by integrated PET/CT imaging.

PURPOSE: To evaluate the relationship between coronary artery calcium (CAC) and coronary vasodilator function. METHODS: We evaluated 136 patients without known coronary artery disease (CAD) undergoing vasodilator stress (82)Rb PET/CT and CAC scoring who showed normal myocardial perfusion. The CAC score, resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR) and coronary vascular resistance were analyzed. RESULTS: Global and regional CAC scores showed significant but weak inverse correlations with hyperemic MBF (r=-0.31 and r=-0.26, p< or =0.0002 respectively) and CFR (r=-0.28 and r=-0.2, p< or =0.001 respectively). With increasing CAC score, there was a modest stepwise decline in CFR on a per-patient basis (1.8+/-0.5 vs 1.7+/-0.5 vs 1.5+/-0.4, p=0.048, with total CAC=0, 1-400 and >400, respectively) and on a per-vessel basis. In multivariable modeling only body mass index and CAC score were predictive of CFR. CONCLUSION: In patients with an intermediate likelihood of, but without overt, CAD, there is a statistically significant but weak inverse correlation between CAC content and coronary vasodilator function. The strength of this association weakens after adjusting CAC scores for age, gender and coronary risk factors. This suggests that CAC and coronary vasodilator function provide biologically different information regarding atherosclerosis.

Quantitative relationship between coronary vasodilator reserve assessed by 82Rb PET imaging and coronary artery stenosis severity.

PURPOSE: The relationship between myocardial blood flow (MBF) and stenosis severity has been determined previously using cyclotron-produced radiotracers such as (15)O-H(2)O and (13)N-ammonia. An attractive alternative to overcome the limitations related to the use of cyclotron might be to use the generator-produced (82)Rb as a flow tracer. The current study was undertaken to investigate the relationship between MBF and coronary vasodilator reserve (CVR) as measured by (82)Rb positron emission tomography (PET) and the percent diameter stenosis as defined by quantitative coronary arteriography. METHODS: We prospectively evaluated 22 individuals: 15 patients (60 +/- 11 years of age) with angiographically documented coronary artery disease (CAD) and seven age-matched (56 +/- 9 years) asymptomatic individuals without risk factors for CAD. Dynamic (82)Rb PET was performed at rest and after dipyridamole vasodilation. MBF, CVR and an index of 'minimal coronary resistance' (MCR) were assessed in each of the three main coronary territories. RESULTS: Rest and stress MBF in regions subtended by vessels with less than 50% diameter stenosis was similar to that of the individuals with no risk factors for CAD. As a result, CVR was also similar in the two groups (1.9, interquartile [IQ] range from 1.7 to 2.7 vs. 2.2, IQ range from 2 to 3.4 respectively, p = 0.09). CVR successfully differentiated coronary lesions with stenosis severity 70% to 89% from those with 50% to 69% stenosis (1, IQ range from 1 to 1.3 vs. 1.7, IQ range from 1.4 to 2), respectively, p = 0.001. In addition, hyperaemic MBF (r (2) = 0.74, p < 0.001), CVR (r (2) = 0.69, p < 0.001) and MCR (r (2) = 0.78, p < 0.001) measurements were inversely and non-linearly correlated to the percent diameter stenosis on angiography. CONCLUSION: MBF and CVR are inversely and non-linearly correlated to stenosis severity. Quantitative (82)Rb PET can be a clinically useful tool for an accurate functional assessment of CAD.

Relationship between CT coronary angiography and stress perfusion imaging in patients with suspected ischemic heart disease assessed by integrated PET-CT imaging.

BACKGROUND: Although computed tomography (CT) coronary angiography (CTA) provides detailed assessments of the anatomic extent of coronary artery disease (CAD), its value for predicting myocardial ischemia is unclear. We examined the value of CTA to identify the presence of ischemia, as determined by stress perfusion imaging, using integrated positron emission tomography (PET)-CT imaging. METHODS AND RESULTS: We studied 110 consecutive patients (median age, 57 years; 55% male) with suspected CAD undergoing stress rubidium 82 myocardial perfusion PET imaging and CTA in the same setting. Increasing degrees of CTA-detected luminal narrowing (<50%, 50%-70%, and >70%) were associated with reduced sensitivity with commensurate improvements in specificity for identifying myocardial ischemia both on a per-vessel basis and on a per-patient basis. Consequently, with increasing degrees of CTA-detected stenosis severity, the positive predictive value increased (14%, 26%, and 53%, respectively, on a per-vessel basis [P < .001] and 29%, 44%, and 77%, respectively, on a per-patient basis [P = .005]), whereas the negative predictive value was unchanged (97%, 97%, and 96%, respectively, on a per-vessel basis [P = not significant (NS)] and 92%, 91%, and 88%, respectively, on a per-patient basis [P = NS]). Receiver operating characteristic analysis revealed no differences between these 3 anatomic criteria (receiver operating characteristic areas of 0.66 +/- 0.07, 0.73 +/- 0.06, and 0.71 +/- 0.07, respectively [P = NS]) for identifying ischemia. Nearly half of significant angiographic stenoses (47%) occurred without evidence of myocardial ischemia, whereas 50% of normal PET studies were associated with some CTA abnormality. CONCLUSIONS: Despite an excellent negative predictive value, CTA is a poor discriminator of patients with myocardial ischemia. Conversely, a normal stress PET study is a poor discriminator of patients without evidence of non-flow-limiting (subclinical) coronary atherosclerosis. These results suggest potentially complementary roles of CT and perfusion imaging in the evaluation of patients with suspected CAD.

Dynamic aortic obstruction in a patient with acute type B dissection.

There are at least 7000 aortic dissections diagnosed in the United States each year. Type B dissections accounted for 38% of cases enrolled in the prospective International Registry of Aortic Dissection. We report a case of a 48-year-old hypertensive woman with an acute type B aortic dissection causing significant dynamic obstruction of the aorta. Intravascular ultrasound of her aorta revealed a mobile intimal flap nearly obliterating the true lumen with each systolic contraction. Simultaneous pressure tracings obtained from her ascending aorta and femoral artery demonstrated a systolic pressure gradient in excess of 100 mm Hg. The patient developed progressive renal failure and ultimately underwent successful operative replacement of the proximal descending thoracic aorta with a Dacron graft. In this case presentation, we highlight the unusual physiology exemplified by this case and explore contemporary management strategies for complicated type B aortic dissection, including surgery and catheter-based techniques.