Quantitative cardiovascular magnetic resonance perfusion imaging identifies reduced flow reserve in microvascular coronary artery disease.

BACKGROUND: Preliminary semi-quantitative cardiovascular magnetic resonance (CMR) perfusion studies have demonstrated reduced myocardial perfusion reserve (MPR) in patients with angina and risk factors for microvascular disease (MVD), however fully quantitative CMR has not been studied. The purpose of this study is to evaluate whether fully quantitative CMR identifies reduced MPR in this population, and to investigate the relationship between epicardial atherosclerosis, left ventricular hypertrophy (LVH), extracellular volume (ECV), and perfusion. METHODS: Forty-six patients with typical angina and risk factors for MVD (females, or males with diabetes or metabolic syndrome) who had no obstructive coronary artery disease by coronary angiography and 20 healthy control subjects underwent regadenoson stress CMR perfusion imaging using a dual-sequence quantitative spiral pulse sequence to quantify MPR. Subjects also underwent T1 mapping to quantify ECV, and computed tomographic (CT) coronary calcium scoring to assess atherosclerosis burden. RESULTS: In patients with risk factors for MVD, both MPR (2.21 [1.95,2.69] vs. 2.93 [2.763.19], p < 0.001) and stress myocardial perfusion (2.65 ± 0.62 ml/min/g, vs. 3.17 ± 0.49 ml/min/g p < 0.002) were reduced as compared to controls. These differences remained after adjusting for age, left ventricular (LV) mass, body mass index (BMI), and gender. There were no differences in native T1 or ECV between subjects and controls. CONCLUSIONS: Stress myocardial perfusion and MPR as measured by fully quantitative CMR perfusion imaging are reduced in subjects with risk factors for MVD with no obstructive CAD as compared to healthy controls. Neither myocardial hypertrophy nor fibrosis accounts for these differences.

Hostility and platelet reactivity in individuals without a history of cardiovascular disease events.

OBJECTIVE: To examine the association between hostility and platelet reactivity in individuals without a prior history of cardiovascular disease (CVD) events. Hostility is associated with incident CVD events, independent of traditional risk factors. Increased platelet reactivity and thrombus formation over a disrupted coronary plaque are fundamental for CVD event onset. METHODS: Hypertensive patients (n = 42) without concomitant CVD event history completed the 50-item Cook-Medley Hostility Scale, and a subset score of 27 items (Barefoot Ho) was derived. We examined the relationship between Barefoot Ho scores and platelet aggregation. We also examined individual components of Barefoot Ho (aggressive responding, cynicism, and hostile affect) and their associations with platelet aggregation. Platelet reactivity, induced by adenosine diphosphate (ADP), was assessed by standard light transmission aggregometry, the current gold standard method of platelet aggregation assessment. RESULTS: Barefoot Ho scores were related significantly to increased rate of platelet aggregation in response to ADP. Of the three Barefoot Ho components, only aggressive responding was associated independently with increased platelet aggregation rate. The strength of these relationships did not diminish after adjusting for several standard CVD risk factors. CONCLUSIONS: These data demonstrate that hostility, particularly the aggressive responding subtype, is associated with platelet reactivity-a key pathophysiological pathway in the onset of CVD events.

Extracellular volume by cardiac magnetic resonance is associated with biomarkers of inflammation in hypertensive heart disease.

OBJECTIVES: Cardiac magnetic resonance (CMR) provides a unique approach to the characterization of hypertensive heart disease (HHD), enabling the measurement of left ventricular mass and expansion of extracellular volume (ECV). Combining plasma biomarkers with CMR could provide potential insights into the pathophysiological mechanisms in ventricular remodelling. METHODS: In this study, we estimated correlations between plasma biomarkers and CMR parameters of HHD. Patients with a history of hypertension with or without left ventricular hypertrophy (LVH) and healthy volunteers (17 hypertensive non-LVH, 13 hypertensive LVH and 11 controls) underwent CMR on a Siemens 1.5T Avanto. T1 mapping was performed before (native T1) and serially after injection of 0.15 mmol/kg gadolinium-DTPA. Mean ECV and left ventricular mass index (LVMI) were determined. Blood samples were obtained and analysed using the Olink CVD 92-plex biomarker panel. RESULTS: Individual groups were compared on the basis of 91 plasma biomarkers using partial least squares discriminant analysis (PLS-DA). ECV and LVMI were correlated with the 91 distinct plasma biomarkers via orthogonal projection to latent structures by partial least square (OPLS) analysis. A two-dimensional PLS-DA explained 49% of the differences between the three groups. OPLS analysis showed that four plasma biomarkers were significantly correlated to both ECV and LVMI, eight were significantly correlated with LVMI only and 11 were significantly correlated to ECV only. CONCLUSION: ECV and LVMI correlate differentially in plasma biomarker patterns. Top predictors of ECV consisted of well established biomarkers of systemic inflammation and metabolic function.

Increased extracellular volume and altered mechanics are associated with LVH in hypertensive heart disease, not hypertension alone.

OBJECTIVES: The goal of this study was to assess the relationship among extracellular volume (ECV), native T1, and systolic strain in hypertensive patients with left ventricular hypertrophy (HTN LVH), hypertensive patients without LVH (HTN non-LVH), and normotensive controls. BACKGROUND: Diffuse myocardial fibrosis in HTN LVH patients, as reflected by increased ECV and native T1, may be an underlying mechanism contributing to increased cardiovascular risk compared with HTN non-LVH subjects and controls. Furthermore, increased diffuse fibrosis in HTN LVH subjects may be associated with reduced peak systolic and early diastolic strain rate compared with the other 2 groups. METHODS: T1 mapping was performed in 20 HTN LVH (mean age, 55 ± 11 years), 23 HTN non-LVH (mean age, 61 ± 12 years), and 22 control subjects (mean age, 54 ± 7 years) on a Siemens 1.5-T Avanto (Siemens Healthcare, Erlangen, Germany) using a previously validated modified look-locker inversion-recovery pulse sequence. T1 was measured pre-contrast and 10, 15, and 20 min after injection of 0.15 mmol/kg gadopentetate dimeglumine, and the mean ECV and native T1 were determined for each subject. Measurement of circumferential strain parameters were performed using cine displacement encoding with stimulated echoes. RESULTS: HTN LVH subjects had higher native T1 compared with controls (p < 0.05). HTN LVH subjects had higher ECV compared with HTN non-LVH subjects and controls (p < 0.05). Peak systolic circumferential strain and early diastolic strain rates were reduced in HTN LVH subjects compared with HTN non-LVH subjects and controls (p < 0.05). Increased levels of ECV and native T1 were associated with reduced peak systolic and early diastolic circumferential strain rate across all subjects. CONCLUSIONS: HTN LVH patients had higher ECV, longer native T1 and associated reduction in peak systolic circumferential strain, and early diastolic strain rate compared with HTN non-LVH and control subjects. Measurement of ECV and native T1 provide a noninvasive assessment of diffuse fibrosis in hypertensive heart disease.

Late gadolinium enhancement on cardiac magnetic resonance predicts adverse cardiovascular outcomes in nonischemic cardiomyopathy: a systematic review and meta-analysis.

BACKGROUND: Late gadolinium enhancement (LGE) by cardiac MR (CMR) is a predictor of adverse cardiovascular outcomes in patients with nonischemic cardiomyopathy (NICM). However, these findings are limited by single-center studies, small sample sizes, and low event rates. We performed a meta-analysis to evaluate the prognostic role of LGE by CMR (LGE-CMR) imaging in patients with NICM. METHODS AND RESULTS: PubMed, Cochrane CENTRAL, and EMBASE were searched for studies looking at the prognostic value of LGE-CMR in patients with NICM. The primary end points included all-cause mortality, heart failure hospitalization, and a composite end point of sudden cardiac death (SCD) or aborted SCD. Pooling of odds ratios was performed using a random-effect model, and annualized event rates were assessed. Data were included from 9 studies with a total of 1488 patients and a mean follow-up of 30 months. Patients had a mean age of 52 years, 67% were men, and the average left ventricular ejection fraction was 37% on CMR. LGE was present in 38% of patients. Patients with LGE had increased overall mortality (odds ratio, 3.27; P<0.00001), heart failure hospitalization (odds ratio, 2.91; P=0.02), and SCD/aborted SCD (odds ratio, 5.32; P<0.00001) compared with those without LGE. The annualized event rates for mortality were 4.7% for LGE+ subjects versus 1.7% for LGE- subjects (P=0.01), 5.03% versus 1.8% for heart failure hospitalization (P=0.002), and 6.0% versus 1.2% for SCD/aborted SCD (P<0.001). CONCLUSIONS: LGE in patients with NICM is associated with increased risk of all-cause mortality, heart failure hospitalization, and SCD. Detection of LGE by CMR has excellent prognostic characteristics and may help guide risk stratification and management in patients with NICM.

Adenosine stress cardiovascular magnetic resonance with variable-density spiral pulse sequences accurately detects coronary artery disease: initial clinical evaluation.

BACKGROUND: Adenosine stress cardiovascular magnetic resonance perfusion imaging can be limited by motion-induced dark-rim artifacts, which may be mistaken for true perfusion abnormalities. A high-resolution variable-density spiral pulse sequence with a novel density compensation strategy has been shown to reduce dark-rim artifacts in first-pass perfusion imaging. We aimed to assess the clinical performance of adenosine stress cardiovascular magnetic resonance using this new perfusion sequence to detect obstructive coronary artery disease. METHODS AND RESULTS: Cardiovascular magnetic resonance perfusion imaging was performed during adenosine stress (140 µg/kg per minute) and at rest on a Siemens 1.5-T Avanto scanner in 41 subjects with chest pain scheduled for coronary angiography. Perfusion images were acquired during injection of 0.1 mmol/kg Gadolinium-diethylenetriaminepentacetate at 3 short-axis locations using a saturation recovery interleaved variable-density spiral pulse sequence. Significant stenosis was defined as >50% by quantitative coronary angiography. Two blinded reviewers evaluated the perfusion images for the presence of adenosine-induced perfusion abnormalities and assessed image quality using a 5-point scale (1 [poor] to 5 [excellent]). The prevalence of obstructive coronary artery disease by quantitative coronary angiography was 68%. The average sensitivity, specificity, and accuracy were 89%, 85%, and 88%, respectively, with a positive predictive value and negative predictive value of 93% and 79%, respectively. The average image quality score was 4.4±0.7, with only 1 study with more than mild dark-rim artifacts. There was good inter-reader reliability with a κ statistic of 0.67. CONCLUSIONS: Spiral adenosine stress cardiovascular magnetic resonance results in high diagnostic accuracy for the detection of obstructive coronary artery disease with excellent image quality and minimal dark-rim artifacts.

Impact of mechanical activation, scar, and electrical timing on cardiac resynchronization therapy response and clinical outcomes.

OBJECTIVES: Using cardiac magnetic resonance (CMR), we sought to evaluate the relative influences of mechanical, electrical, and scar properties at the left ventricular lead position (LVLP) on cardiac resynchronization therapy (CRT) response and clinical events. BACKGROUND: CMR cine displacement encoding with stimulated echoes (DENSE) provides high-quality strain for overall dyssynchrony (circumferential uniformity ratio estimate [CURE] 0 to 1) and timing of onset of circumferential contraction at the LVLP. CMR DENSE, late gadolinium enhancement, and electrical timing together could improve upon other imaging modalities for evaluating the optimal LVLP. METHODS: Patients had complete CMR studies and echocardiography before CRT. CRT response was defined as a 15% reduction in left ventricular end-systolic volume. Electrical activation was assessed as the time from QRS onset to LVLP electrogram (QLV). Patients were then followed for clinical events. RESULTS: In 75 patients, multivariable logistic modeling accurately identified the 40 patients (53%) with CRT response (area under the curve: 0.95 [p < 0.0001]) based on CURE (odds ratio [OR]: 2.59/0.1 decrease), delayed circumferential contraction onset at LVLP (OR: 6.55), absent LVLP scar (OR: 14.9), and QLV (OR: 1.31/10 ms increase). The 33% of patients with CURE <0.70, absence of LVLP scar, and delayed LVLP contraction onset had a 100% response rate, whereas those with CURE ≥0.70 had a 0% CRT response rate and a 12-fold increased risk of death; the remaining patients had a mixed response profile. CONCLUSIONS: Mechanical, electrical, and scar properties at the LVLP together with CMR mechanical dyssynchrony are strongly associated with echocardiographic CRT response and clinical events after CRT. Modeling these findings holds promise for improving CRT outcomes.

Coronary microvascular dysfunction in women: an overview of diagnostic strategies.

Coronary microvascular dysfunction (CMD) also known as syndrome X, is characterized by typical anginal symptoms, evidence of myocardial ischemia on non-invasive testing and normal to minimal coronary disease on coronary angiography. It has a female preponderance and has been detected in up to 50% of women presenting with chest pain symptoms. Definitive diagnosis of CMD is critical as recent evidence suggests that women with this condition are at increased risk of cardiovascular events in the future. Invasive coronary reactivity testing on coronary angiography is considered to be the 'gold standard' for diagnosis of CMD. Non-invasive imaging techniques such as PET and cardiac magnetic resonance hold promise for detection of CMD in the future.

A novel and simple protocol for the validation of home blood pressure monitors in clinical practice.

BACKGROUNDS: Although the European Society of Hypertension International Protocol for the validation of blood pressure (BP) measuring devices has simplified the validation protocol, it is still not feasible for use in routine clinical practice. OBJECTIVES: We sought to devise a method for validating individual home blood pressure (HBP) monitors that is simple enough for use in routine clinical practice. METHODS: We consecutively enrolled 92 hypertensive patients (mean age: 63.2 ± 14.6 years) from the hypertension clinic at the Columbia University Medical Center. Five sequential same-arm BP readings were recorded by a physician: first (D1), second (D2), and fourth (D3) using an HBP device; the third (M1) and fifth (M2) readings were taken manually using a mercury sphygmomanometer. Analyses focused on the absolute values of the differences in the BP values. In step 1, differences D2-M1, M1-D3, and D3-M2 were calculated and if two of three BP differences were within 5 mmHg (or 10 mmHg), the monitor 'passed'. When a monitor failed step 1, if either the difference between M1 and the average of D2 and D3, or the difference between D3 and the average of M1 and M2 was within 5 mmHg (or 10 mmHg), it was judged to have 'passed'. RESULTS: We used only systolic blood pressure to simplify the protocol. In step 1, the number of monitors in which two of three BP differences were within 5 mmHg was 43 (46.7%) and those within 10 mmHg was 73 (79.4%) of 92 total monitors. Of those that failed the 5 mmHg criterion of step 1 (N = 49), 20 passed step 2. Therefore, a total of 63 monitors (68.5%) fulfilled the 5 mmHg criteria. Of 19 monitors that failed step 1 using the 10 mmHg criterion, 12 fulfilled the 10 mmHg criterion for step 2, resulting in 85 of the 92 (92.4%) monitors passing the test. CONCLUSION: This simplified validation protocol may be of value for the routine evaluation of HBP monitors in clinical practice.

Correlations between different measures of clinic, home, and ambulatory blood pressure in hypertensive patients.

OBJECTIVES: It is not well known how clinic, home, and ambulatory measures of blood pressure (BP) correlate with each other. We performed this study to clarify the level of agreement among these different BP measures. MATERIALS AND METHODS: We enrolled 56 hypertensive patients (mean age: 60 ± 14 years; 54% were females). The study consisted of three clinic visits, self-monitoring of home BP between visits, and ambulatory blood pressure (ABP) monitoring at the second visit. Patients were given a home BP monitor programmed to automatically take three consecutive readings at fixed intervals of 1 min. The associations between clinic BP (mercury sphygmomanometer and HEM-5001), home BP (the average of morning and evening, second and third BP readings), and average awake ABP were compared using the intraclass correlation for agreement and Bland-Altman plots. RESULTS: The averages of clinic sphygmomanometer, clinic HEM-5001, awake ABP, and home BP were 129 of 77, 131 of 76, 131 of 79, and 133 of 77 mmHg, respectively. Clinic BP by HEM-5001 was strongly correlated with that of mercury sphygmomanometer. Home systolic blood pressure was moderately correlated with awake ABP, but mercury diastolic blood pressure (DBP) was more closely correlated with awake DBP than home DBP. CONCLUSION: Clinic BP measured with the automated monitor could be used as an alternative for the evaluation of BP in the office. Under rigorously standardized conditions, clinic and home BP could be used as an alternative to awake ABP.

Preventing misdiagnosis of ambulatory hypertension: algorithm using office and home blood pressures.

OBJECTIVES: An algorithm for making a differential diagnosis between sustained and white coat hypertension (WCH) has been proposed - patients with office hypertension undergo home blood pressure monitoring (HBPM) and those with normal HBP levels undergo ambulatory blood pressure monitoring (ABPM). We tested whether incorporating an upper office blood pressure (OBP) cut-off in the algorithm, higher than the traditional 140/90 mmHg, reduces the need for HBPM and ABPM. METHODS: Two hundred twenty-nine normotensive and untreated mildly hypertensive participants (mean age 52.5 +/- 14.6 years, 54% female participants) underwent OBP measurements, HBPM, and 24-h ABPM. Using the algorithm, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) for sustained hypertension and WCH were assessed. We then modified the algorithm utilizing a systolic and diastolic OBP cut-off at a specificity of 95% for ambulatory hypertension - those with office hypertension but OBP levels below the upper cut-off underwent HBPM and subsequent ABPM, if appropriate. RESULTS: Using the original algorithm, sensitivity and PPV for sustained hypertension were 100% and 93.8%, respectively. Despite a specificity of 44.4%, NPV was 100%. These values correspond to specificity, NPV, sensitivity, and PPV for WCH, respectively. Using the modified algorithm, the diagnostic accuracy for sustained hypertension and WCH did not change. However, far fewer participants needed HBPM (29 vs. 84) and ABPM (8 vs. 15). CONCLUSION: In this sample, the original and modified algorithms are excellent at diagnosing sustained hypertension and WCH. However, the latter requires far fewer participants to undergo HBPM and ABPM. These findings have important implications for the cost-effective diagnosis of sustained hypertension and WCH.

What is the optimal interval between successive home blood pressure readings using an automated oscillometric device?

OBJECTIVES: To clarify whether a shorter interval between three successive home blood pressure (HBP) readings (10 s vs. 1 min) taken twice a day gives a better prediction of the average 24-h BP and better patient compliance. DESIGN: We enrolled 56 patients from a hypertension clinic (mean age: 60 +/- 14 years; 54% female patients). The study consisted of three clinic visits, with two 4-week periods of self-monitoring of HBP between them, and a 24-h ambulatory BP monitoring at the second visit. Using a crossover design, with order randomized, the oscillometric HBP device (HEM-5001) could be programmed to take three consecutive readings at either 10-s or 1-min intervals, each of which was done for 4 weeks. Patients were asked to measure three HBP readings in the morning and evening. All the readings were stored in the memory of the monitors. RESULTS: The analyses were performed using the second-third HBP readings. The average systolic BP/diastolic BP for the 10-s and 1-min intervals at home were 136.1 +/- 15.8/77.5 +/- 9.5 and 133.2 +/- 15.5/76.9 +/- 9.3 mmHg (P = 0.001/0.19 for the differences in systolic BP and diastolic BP), respectively. The 1-min BP readings were significantly closer to the average of awake ambulatory BP (131 +/- 14/79 +/- 10 mmHg) than the 10-s interval readings. There was no significant difference in patients' compliance in taking adequate numbers of readings at the different time intervals. CONCLUSION: The 1-min interval between HBP readings gave a closer agreement with the daytime average BP than the 10-s interval.

Changes in home versus clinic blood pressure with antihypertensive treatments: a meta-analysis.

Home blood pressure (HBP) monitoring is recommended for assessing the effects of antihypertensive treatment, but it is not clear how the treatment-induced changes in HBP compare with the changes in clinic blood pressure (CBP). We searched PubMed using the terms "home or self-measured blood pressure," and selected articles in which the changes in CBP and HBP (using the upper arm oscillometric method) induced by antihypertensive drugs were presented. We performed a systematic review of 30 articles published before March 2008 that included a total of 6794 subjects. As there was significant heterogeneity in most of the outcomes, a random effects model was used for the meta-analyses. The mean changes (+/-SE) in CBP and HBP (systolic/diastolic) were -15.2+/-0.03/-10.3+/-0.03 mm Hg and -12.2+/-0.04/-8.0+/-0.04 mm Hg respectively, although there were wide varieties of differences in the reduction between HBP and CBP. The reductions in CBP were correlated with those of HBP (systolic BP; r=0.66, B=0.48, diastolic BP; r=0.71, B=0.52, P<0.001). In 7 studies that also included 24-hour BP monitoring, the reduction of HBP was greater than that of 24-hour BP in systolic (HBP; -12.6+/-0.06 mm Hg, 24-hour BP; -11.9+/-0.04 mm Hg, P<0.001). In 5 studies that included daytime and nighttime systolic BP separately, HBP decreased 15% more than daytime ambulatory BP and 30% more than nighttime ambulatory BP. In conclusion, HBP falls approximately 20% less than CBP with antihypertensive treatments. Daytime systolic BP falls 15% less and nighttime systolic BP falls 30% less than home systolic BP.