Lower Myocardial Perfusion Reserve Index Research Articles

Arterial stiffness assessment in coronary microvascular dysfunction and heart failure with preserved ejection fraction: An initial report from the WISE-CVD continuation study

BackgroundHeart failure with preserved ejection fraction (HFpEF) is the most common cardiac complication in patients with coronary microvascular dysfunction (CMD), yet its underlying pathways remain unclear. Aortic pulse-wave velocity (aPWV) is an indicator of large artery stiffness and a predictor for cardiovascular disease. However, aPWV in CMD and HFpEF is not well characterized and may provide understanding of disease progression. MethodsAmong participants without obstructive coronary artery disease, we evaluated 51 women with suspected CMD and 20 women and men with evidence of HFpEF. All participants underwent aPWV measurement (SphygmoCor, Atcor Medical) with higher aPWV indicating greater vascular stiffness. Cardiac magnetic resonance imaging (CMRI) assessed left ventricular (LV) ejection fraction, CMD via myocardial perfusion reserve index (MPRI), and ventricular remodeling via LV mass-volume ratio. . Statistical analysis was performed using Wilcoxon rank sum tests, Pearson correlations and linear regression analysis. ResultsCompared to the suspected CMD group, the HFpEF participants were older (65 ± 12 vs 56 ± 11 yrs., p = 0.002) had higher BMI (31.0 ± 4.3 vs 27.8 ± 6.7 kg/m2, p = 0.013), higher aPWV (10.5 ± 2.0 vs 8.0 ± 1.6 m/s, p = 0.05) and lower MPRI (1.5 ± 0.3 vs1.8 ± 0.3, p = 0.02), but not remodeling. In a model adjusted for cardiovascular risk factors, the HFpEF group had a lower LVEF (estimate −4.78, p = 0.0437) than the suspected CMD group. ConclusionsHFpEF participants exhibit greater arterial stiffness and lower myocardial perfusion reserve, with lower LVEF albeit not remodeling, compared to suspected CMD participants. These findings suggest arterial stiffness may contribute to progression from CMD to HFpEF. Prospective work is needed and ongoing.

Autoimmune rheumatic diseases in women with coronary microvascular dysfunction: a report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project.

While autoimmune rheumatic diseases (ARDs) have been linked with coronary microvascular dysfunction (CMD), the relationship between ARD and CMD in women with signs and symptoms of ischemia and no obstructive arteries (INOCA) are not well described. We hypothesized that among women with CMD, those with ARD history have greater angina, functional limitations, and myocardial perfusion compromise compared to those without ARD history. Women with INOCA and confirmed CMD by invasive coronary function testing were included from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project (NCT00832702). Seattle Angina Questionnaire (SAQ), Duke Activity Status Index (DASI), and cardiac magnetic resonance myocardial perfusion reserve index (MPRI) were collected at baseline. Chart review was performed to confirm self-reported ARD diagnosis. Of the 207 women with CMD, 19 (9%) had a confirmed history of ARD. Compared to those without ARD, women with ARD were younger (p = 0.04). In addition, they had lower DASI-estimated metabolic equivalents (p = 0.03) and lower MPRI (p = 0.008) but similar SAQ scores. There was a trend towards increased nocturnal angina and stress-induced angina in those with ARD (p = 0.05 for both). Invasive coronary function variables were not significantly different between groups. Among women with CMD, women with a history of ARD had lower functional status and worse myocardial perfusion reserve compared to women without ARD. Angina-related health status and invasive coronary function were not significantly different between groups. Further studies are warranted to understand mechanisms contributing to CMD among women with ARDs with INOCA.

Sex differences in contributors to coronary microvascular dysfunction.

Coronary microvascular dysfunction (CMD) has differences in prevalence and presentation between women and men; however, we have limited understanding about underlying contributors to sex differences in CMD. Myocardial perfusion reserve index (MPRI), as semi-quantitative measure of myocardial perfusion derived from cardiac magnetic resonance (CMR) imaging has been validated as a measure of CMD. We sought to understand the sex differences in the relations between the MPRI and traditional measures of cardiovascular disease by CMR. A retrospective analysis of a single-center cohort of patients receiving clinical stress CMR from 2015 to 2022 was performed. Patients with calculated MPRI and no visible perfusion defects consistent with obstructive epicardial coronary disease were included. We compared associations between MPRI versus traditional cardiovascular risk factors and markers of cardiac structure/function in sex-stratified populations using univariable and multivariable regression models. A total of 229 patients [193 female, 36 male, median age 57 (47-67) years] were included in the analysis. In the female population, no traditional cardiovascular risk factors were associated with MPRI, whereas in the male population, diabetes (β: -0.80, p = 0.03) and hyperlipidemia (β: -0.76, p = 0.006) were both associated with reduced MPRI in multivariable models. Multivariable models revealed significant associations between reduced MPRI and increased ascending aortic diameter (β: -0.42, p = 0.005) and T1 times (β: -0.0056, p = 0.03) in the male population, and increased T1 times (β: -0.0037, p = 0.006) and LVMI (β: -0.022, p = 0.0003) in the female population. The findings suggest different underlying pathophysiology of CMD in men versus women, with lower MPRI in male patients fitting a more "traditional" atherosclerotic profile.

Surveillance of Chronic Graft Failure Utilizing Cardiac Magnetic Resonance Imaging in Pediatric Heart Transplantation

<h3>Purpose</h3> The cause of chronic graft failure (CGF) in heart transplantation (HT) is multifactorial including cardiac allograft vasculopathy (CAV) and rejection. Previous studies have shown that endomyocardial biopsy (EMB) can detect fibrosis and microvessel disease (MVD) in patients with CGF. We sought to evaluate associations between, 1. CAV, 2. Historical moderate to severe (M/S) rejection, and 3. Histopathologic changes of CGF on EMB with cardiac magnetic resonance imaging (CMR) parameters to assess its use as a non-invasive surveillance modality for CGF in pediatric heart transplant patients (PHT). <h3>Methods</h3> Retrospective evaluation of PHT who underwent CMR between 9/2015 and 10/2021 was performed. Those with EMB within 6 months of CMR were included; PHT with M/S rejection on EMB were excluded. CAV was assessed per ISHLT guidelines. Historical M/S rejection, included PHT with a history of ACR >2R or AMR>2. CMR included assessment of cardiac function, myocardial edema (T2 mapping), fibrosis (pre-contrast T1 mapping and extracellular volume fraction), and myocardial perfusion reserve index (MPRi) calculated from stress perfusion imaging. On EMB, fibrosis was qualitatively scored on a scale of 0-5 and MVD was quantified as number of capillaries with stenotic wall thickening per fields of view. Wilcoxon rank sum test or Spearman rank correlation investigated relationships between presence of CAV, historical M/S rejection, EMB and CMR findings. Unadjusted p-values are reported. <h3>Results</h3> Forty-one PHT with median age at CMR of 15.7 years (11.6,19.3) and time from HT of 6.4 years (4.1,11.0) were studied. CAV was present in 9/41(22.0%), although only 2/9 had greater than CAV 1. Historical M/S rejection was present in 14/41 (34.2%). Presence of CAV was associated with lower LVEF (60% vs 56%; p=0.03), higher peak T2 (53 vs 56 ms; p=0.04). Historical M/S rejection was associated with higher global T2 (47 vs 49 ms; p=0.01) and peak T2 (53 vs 57 ms; p=0.02). Higher fibrosis score on EMB was associated with lower MPRi on CMR (rho= -0.35; p=0.04). <h3>Conclusion</h3> Abnormalities in CMR parameters are noted in those with CAV, historical M/S rejection, and greater fibrosis on EMB in a relatively healthy PHT cohort. Longitudinal follow up studies in larger cohorts may aid in further refining the role of CMR in CGF surveillance.

Coronary artery spasm and impaired myocardial perfusion in patients with ANOCA: Predictors from a multimodality study using stress CMR and acetylcholine testing

BackgroundFunctional coronary disorders such as coronary spasm and microvascular dysfunction (including microvascular spasm and impaired microvascular dilatation) are frequent findings among patients with angina and non-obstructed coronary arteries (ANOCA). In this study, we investigated a potential association of coronary spasm and myocardial perfusion abnormalities as well as predictors of such functional coronary disorders in ANOCA patients using a multimodality diagnostic strategy including adenosine stress CMR and intracoronary acetylcholine testing. MethodsWe enrolled 129 patients with ANOCA who underwent acetylcholine testing and adenosine stress perfusion CMR. Patients were allocated to 3 groups according to their spasm testing result with regard to standardized COVADIS criteria: 1) epicardial spasm, 2) microvascular spasm, and 3) no spasm. The myocardial perfusion reserve index (MPRI) was semiquantitatively determined from adenosine stress perfusion CMR. Multivariate regression analyses were performed to identify predictors of coronary functional disorders. ResultsPatients with epicardial spasm had lower MPRI than patients without, whereas MPRI was preserved in patients with microvascular spasm. Multivariate analyses revealed age, previous myocardial infarction, LVEF and epicardial spasm as independent predictors of diminished MPRI, whereas previous PCI was associated with epicardial spasm, and female sex was a strong predictor of microvascular spasm. ConclusionsOur results demonstrate coexistence of different functional coronary disorder endotypes involving the macro- and microvascular level of the coronary circulation in patients with ANOCA. We demonstrate that epicardial spasm is associated with diminished myocardial perfusion reserve and report further predictors of coronary functional disorders.

Cardiac magnetic resonance imaging myocardial perfusion reserve index in heart transplant patients

ObjectiveTo compare the myocardial perfusion reserve index (MPRI) measured during stress cardiac magnetic resonance imaging (MRI) with regadenoson in patients with heart transplants versus in patients without heart transplants. Material and methodsWe retrospectively compared 20 consecutive asymptomatic heart transplant patients without suspicion of microvascular disease who underwent stress cardiac MRI with regadenoson and coronary computed tomography angiography (CTA) to rule out cardiac allograft vasculopathy versus 16 patients without transplants who underwent clinically indicated stress cardiac MRI who were negative for ischemia and had no signs of structural heart disease. We estimated MPRI semiquantitatively after calculating the up-slope of the first-pass enhancement curve and dividing the value obtained during stress by the value obtained at rest. We compared MPRI in the two groups. Patients with positive findings for ischemia on stress cardiac MRI or significant coronary stenosis on coronary CTA were referred for conventional coronary angiography. ResultsMore than half the patients remained asymptomatic during the stress test. Stress cardiac MRI was positive for ischemia in two heart transplant patients; these findings were confirmed at coronary CTA and at conventional coronary angiography. Patients with transplants had lower end-diastolic volume index (59.3 ± 15.2 ml/m2 vs. 71.4 ± 15.9 ml/m2 in those without transplants, p = 0.03), lower MPRI (1.35 ± 0.19 vs. 1.6 ± 0.28 in those without transplants, p = 0.003), and a less pronounced hemodynamic response to regadenoson (mean increase in heart rate 13.1 ± 5.4 bpm vs. 28.5 ± 8.9 bpm in those without transplants, p < 0.001). ConclusionStress cardiac MRI with regadenoson is safe. In the absence of epicardial coronary artery disease, patients with heart transplants have lower MPRI than patients without transplants, suggesting microvascular disease. The hemodynamic response to regadenoson is less pronounced in patients with heart transplants than in patients without heart transplants.

Adenosine stress native T1 mapping demonstrates impaired myocardial perfusion reserve in non-ischemic dilated cardiomyopathy

Abstract Background Impaired myocardial perfusion reserve has been demonstrated in non-ischemic dilated cardiomyopathy (NIDCM) by positron emission tomography (PET) and adenosine-stress first-pass perfusion cardiac magnetic resonance (CMR) imaging. Adenosine stress native T1 mapping is a novel CMR technique able to assess myocardial perfusion without the use of contrast agents. The aim of the present study was to determine the clinical utility of this novel CMR technique in NIDCM. Methods A total of 20 consecutive patients (mean age 61±12 years, 80% males) with diagnosis of NIDCM who consented to be enrolled in the UHSM CMR registry were included in the present study. CMR at 3T including 1. cine imaging for the assessment of LV volumes, mass and global longitudinal strain (GLS) by tissue-tracking imaging; 2. rest and stress (adenosine 140 mcg/kg/min) MOLLI T1 mapping of mid-ventricular slice for the assessment of rest and stress T1 values and T1 reactivity (ΔT1%); 3. first-pass perfusion imaging for the assessment of myocardial perfusion reserve index (MPRI) and 4. late gadolinium enhancement (LGE) imaging for the assessment of myocardial replacement fibrosis, was performed. Twenty control patients without history of known coronary artery disease and evidence of reversible ischemia or previous myocardial infarct on CMR imaging were included for comparison purposes. Results NIDCM patients had significantly higher native T1 value (1263±47 ms vs. 1234±38 ms, p=0.031), significantly lower ΔT1% (3.2±1.5% vs. 5.7±1.7%, p&amp;lt;0.001, Figure A), significantly lower MPRI (1.32±0.18 vs. 1.67±0.13, p&amp;lt;0.001) and significantly impaired GLS (−10±4% vs. −16±2%, p&amp;lt;0.001) as compared to controls. A significant strong relation between ΔT1% and MPRI (β=0.76, p&amp;lt;0.001, Figure B) and significant moderate relation between ΔT1% and GLS (β=−0.54, p&amp;lt;0.001) were observed. Conclusion T1 reactivity, myocardial perfusion reserve and GLS are significantly reduced in NIDCM patients compared to controls. Adenosine stress T1 mapping holds promise for detection of impaired myocardial perfusion reserve in NIDCM without the requirement for contrast agents. Funding Acknowledgement Type of funding source: None

Valoración del índice de reserva de perfusión miocárdica por resonancia magnética en pacientes con trasplante cardíaco

ObjectiveTo compare the myocardial perfusion reserve index (MPRI) measured during stress cardiac magnetic resonance imaging (MRI) with regadenoson in patients with heart transplants versus in patients without heart transplants. Material and methodsWe retrospectively compared 20 consecutive asymptomatic heart transplant patients without suspicion of microvascular disease who underwent stress cardiac MRI with regadenoson and coronary computed tomography angiography (CTA) to rule out cardiac allograft vasculopathy versus 16 patients without transplants who underwent clinically indicated stress cardiac MRI who were negative for ischemia and had no signs of structural heart disease. We estimated MPRI semiquantitatively after calculating the up-slope of the first-pass enhancement curve and dividing the value obtained during stress by the value obtained at rest. We compared MPRI in the two groups. Patients with positive findings for ischemia on stress cardiac MRI or significant coronary stenosis on coronary CTA were referred for conventional coronary angiography. ResultsMore than half the patients remained asymptomatic during the stress test. Stress cardiac MRI was positive for ischemia in two heart transplant patients; these findings were confirmed at coronary CTA and at conventional coronary angiography. Patients with transplants had lower end-diastolic volume index (59.3±15.2 ml/m2 vs. 71.4±15.9 ml/m2 in those without transplants, p=0.03), lower MPRI (1.35±0.19 vs. 1.6±0.28 in those without transplants, p=0.003), and a less pronounced hemodynamic response to regadenoson (mean increase in heart rate 13.1±5.4 bpm vs. 28.5±8.9 bpm in those without transplants, p <0.001). ConclusionStress cardiac MRI with regadenoson is safe. In the absence of epicardial coronary artery disease, patients with heart transplants have lower MPRI than patients without transplants, suggesting microvascular disease. The hemodynamic response to regadenoson is less pronounced in patients with heart transplants than in patients without heart transplants.

P875Myocardial perfusion reserve assessment in patients with angina pectoris and suspected coronary spasm

Abstract Background Patients with signs and symptoms of myocardial ischemia yet unobstructed coronary arteries represent a diagnostic and therapeutic challenge. Coronary vasomotor disorders such as coronary epicardial or microvascular spasm are frequently found among these patients. They can be diagnosed using intracoronary acetylcholine testing (ACH-test). It has been shown that patients with epicardial spasm have a worse prognosis compared to patients with microvascular spasm. The reasons for this finding are however not apparent. We speculated in this study that patients with epicardial spasm have a worse vasomotor dysfunction compared to patients with microvascular spasm or normal ACH-test. To assess this hypothesis all patients in this study not only underwent ACH-testing but in addition also adenosine stress perfusion cardiac MRI (CMR) with calculation of the myocardial perfusion reserve index (MPRI). The latter method allows for assessment of vasodilatory function compared to the vasoconstrictor assessment using acetylcholine. Methods Between 2012 and 2016, 129 consecutive patients (mean age 64±13 years, 46% female) with signs and symptoms of myocardial ischemia yet unobstructed coronary arteries were enrolled in this study. All patients underwent ACH-testing as well as adenosine stress perfusion CMR. According to the results of the acetylcholine test, patients were allocated to 3 groups: a) epicardial spasm (angina, ischemic ECG changes and &gt;75% coronary diameter reduction), b) microvascular spasm (angina, ischemic ECG changes and &lt;75% coronary diameter reduction) and c) no evidence of coronary artery spasm. CMR-derived MPRI was calculated semiquantitatively from myocardial signal intensity-over-time curves of adenosine stress and rest perfusion. Results Epicardial and microvascular spasm was found in 31 (24%) and 69 (53%) patients, respectively, while 29 (22%) patients had no evidence of coronary spasm on ACH-testing. Women were more likely to have microvascular spasm than men (68% vs. 36%, p&lt;0.001). The prevalence of epicardial spasm did not significantly differ between female and male patients (18% vs. 31%, p=0.08). MPRI was similar in patients with microvascular spasm compared to patients without spasm (1.30 vs. 1.27, p=0.43). However, patients with epicardial spasm had significantly lower MPRI than patients without spasm (1.16 vs. 1.30, p&lt;0.05) or those with microvascular spasm (1.16 vs. 1.27, p&lt;0.05). Conclusion MPRI determined by stress perfusion CMR was significantly reduced in patients with epicardial spasm compared to those with microvascular spasm or normal ACH-test. This could indicate that patients with epicardial spasm have a more generalized coronary vasomotor disorder compared to other patients. This may be the reason for the worse outcome observed and could lead to more aggressive medical therapy and closer follow-up. Acknowledgement/Funding This work was funded by the Robert-Bosch-Stiftung, Stuttgart, Germany and the Berthold-Leibinger-Stiftung, Ditzingen, Germany.

Left ventricular concentric remodelling and functional impairment in women with ischaemia with no obstructive coronary artery disease and intermediate coronary flow reserve: a report from the WISE-CVD study.

Women with evidence of ischaemia but no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD). Although invasively measured coronary flow reserve (CFR) is useful for the diagnosis of CMD, intermediate CFR values are often found of uncertain significance. We investigated myocardial flow reserve and left ventricular (LV) structural and functional remodelling in women with suspected INOCA and intermediate CFR. Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study participants who had invasively measured intermediate CFR of 2.0≤ CFR ≤3.0 (n = 125) were included for this analysis. LV strain, peak filling rate (PFR) and myocardial perfusion reserve index (MPRI) were obtained by cardiac magnetic resonance imaging. Participants were divided: (i) Group 1 (n = 66) high MPRI ≥ 1.8, and (ii) Group 2 (n = 59) low MPRI < 1.8. The mean age was 54 ± 12 years and CFR was 2.46 ± 0.27. MPRI was significantly different but CFR did not differ between groups. LV relative wall thickness (RWT) trended higher in Group 2 and circumferential peak systolic strain and early diastolic strain rate were lower (P = 0.039 and P = 0.035, respectively), despite a similar LV ejection fraction and LV mass. PFR was higher in Group 1 and LV RWT was negatively related to PFR (r = -0.296, P = 0.001). In women with suspected INOCA and intermediate CFR, those with lower MPRI had a trend towards more adverse remodelling and impaired diastolic LV function compared with those with higher MPRI. CFR was similar between the two groups. These findings provide evidence that both coronary microvessel vasomotion and structural and functional myocardial remodelling contribute to CMD.

Impact of caffeine on myocardial perfusion reserve assessed by semiquantitative adenosine stress perfusion cardiovascular magnetic resonance

BackgroundAdenosine is used in stress perfusion cardiac imaging to reveal myocardial ischemia by its vasodilator effects. Caffeine is a competitive antagonist of adenosine. However, previous studies reported inconsistent results about the influence of caffeine on adenosine's vasodilator effect. This study assessed the impact of caffeine on the myocardial perfusion reserve index (MPRI) using adenosine stress cardiovascular magnetic resonance imaging (CMR). Moreover, we sought to evaluate if the splenic switch-off sign might be indicative of prior caffeine consumption.MethodsSemiquantitative perfusion analysis was performed in 25 patients who underwent: 1) caffeine-naïve adenosine stress CMR demonstrating myocardial ischemia and, 2) repeat adenosine stress CMR after intake of caffeine. MPRI (global; remote and ischemic segments), and splenic perfusion ratio (SPR) were assessed and compared between both exams.ResultsGlobal MPRI after caffeine was lower vs. caffeine-naïve conditions (1.09 ± 0.19 vs. 1.24 ± 0.19; p < 0.01). MPRI in remote myocardium decreased by caffeine (1.24 ± 0.19 vs. 1.49 ± 0.19; p < 0.001) whereas MPRI in ischemic segments (0.89 ± 0.18 vs. 0.95 ± 0.23; p = 0.23) was similar, resulting in a lower MPRI ratio (=remote/ischemic segments) after caffeine consumption vs. caffeine-naïve conditions (1.41 ± 0.19 vs. 1.64 ± 0.35, p = 0.01). The SPR was unaffected by caffeine (SPR 0.38 ± 0.19 vs. 0.38 ± 0.18; p = 0.92).ConclusionCaffeine consumption prior to adenosine stress CMR results in a lower global MPRI, which is driven by the decreased MPRI in remote myocardium and underlines the need of abstinence from caffeine. The splenic switch-off sign is not affected by prior caffeine intake.

Ineffective and prolonged apical contraction is associated with chest pain and ischaemia in apical hypertrophic cardiomyopathy

To investigate the hypothesis that persistence of apical contraction into diastole is linked to reduced myocardial perfusion and chest pain. Apical hypertrophic cardiomyopathy (HCM) is defined by left ventricular (LV) hypertrophy predominantly of the apex. Hyperdynamic contractility resulting in obliteration of the apical cavity is often present. Apical HCM can lead to drug-refractory chest pain. We retrospectively studied 126 subjects; 76 with apical HCM and 50 controls (31 with asymmetrical septal hypertrophy (ASH) and 19 with non-cardiac chest pain and culprit free angiograms and structurally normal hearts). Perfusion cardiac magnetic resonance imaging (CMR) scans were assessed for myocardial perfusion reserve index (MPRi), late gadolinium enhancement (LGE), LV volumes (muscle and cavity) and regional contractile persistence (apex, mid and basal LV). In apical HCM, apical MPRi was lower than in normal and ASH controls (p<0.05). In apical HCM, duration of contractile persistence was associated with lower MPRi (p<0.01) and chest pain (p<0.05). In multivariate regression, contractile persistence was independently associated with chest pain (p<0.01) and reduced MPRi (p<0.001). In apical HCM, regional contractile persistence is associated with impaired myocardial perfusion and chest pain. As apical myocardium makes limited contributions to stroke volume, apical contractility is also largely ineffective. Interventions to reduce apical contraction and/or muscle mass are potential therapies for improving symptoms without reducing cardiac output.

Cardiac Magnetic Resonance Myocardial Perfusion Reserve Index Is Reduced in Women With Coronary Microvascular Dysfunction

Background— Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD), diagnosed by invasive coronary reactivity testing (CRT). Although traditional noninvasive stress imaging is often normal in CMD, cardiac MRI may be able to detect CMD in this population. Methods and Results— Vasodilator stress cardiac MRI was performed in 118 women with suspected CMD who had undergone CRT and 21 asymptomatic reference subjects. Semi-quantitative evaluation of the first-pass perfusion images was completed to determine myocardial perfusion reserve index (MPRI). The relationship between CRT findings and MPRI was examined by Pearson correlations, logistic regression, and sensitivity/specificity. Symptomatic women had lower mean pharmacological stress MPRI compared with reference subjects (1.71±0.43 versus 2.23±0.37; P &lt;0.0001). Lower MPRI was predictive of ≥1 abnormal CRT variables (odds ratio =0.78 [0.70, 0.88], P &lt;0.0001, c-statistic 0.78 [0.68, 0.88]). An MPRI threshold of 1.84 predicted CRT abnormality with sensitivity 73% and specificity 74%. Conclusions— Noninvasive cardiac MRI MPRI can detect CMD defined by invasive CRT. Further work is aimed to optimize the noninvasive identification and management of CMD patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00832702.

Mechanistic Insights and Characterization of Sickle Cell Disease–Associated Cardiomyopathy

Cardiovascular disease is an important cause of morbidity and mortality in sickle cell disease (SCD). We sought to characterize sickle cell cardiomyopathy using multimodality noninvasive cardiovascular testing and identify potential causative mechanisms. Stable adults with SCD (n=38) and healthy controls (n=13) prospectively underwent same day multiparametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator first pass myocardial perfusion, and late gadolinium enhancement imaging), transthoracic echocardiography, and applanation tonometry. Compared with controls, patients with SCD had severe dilation of the left ventricle (124±27 vs 79±12 mL/m(2)), right ventricle (127±28 vs 83±14 mL/m(2)), left atrium (65±16 vs 41±9 mL/m(2)), and right atrium (78±17 vs 56±17 mL/m(2); P<0.01 for all). Patients with SCD also had a 21% lower myocardial perfusion reserve index than control subjects (1.47±0.34 vs 1.87±0.37; P=0.034). A significant subset of patients with SCD (25%) had evidence of late gadolinium enhancement, whereas only 1 patient had evidence of myocardial iron overload. Diastolic dysfunction was present in 26% of patients with SCD compared with 8% in controls. Estimated filling pressures (E/e', 9.3±2.7 vs 7.3±2.0; P=0.0288) were higher in patients with SCD. Left ventricular dilation and the presence of late gadolinium enhancement were inversely correlated to hepatic T2* times (ie, hepatic iron overload because of frequent blood transfusions; P<0.05 for both), whereas diastolic dysfunction and increased filling pressures were correlated to aortic stiffness (augmentation pressure and index, P<0.05 for all). Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some patients myocardial fibrosis, abnormal perfusion reserve, diastolic dysfunction, and only rarely myocardial iron overload. Left ventricular dilation and myocardial fibrosis are associated with increased blood transfusion requirements, whereas left ventricular diastolic dysfunction is predominantly correlated with increased aortic stiffness. http://www.clinicaltrials.gov. Unique identifier: NCT01044901.

Impaired myocardial perfusion reserve and fibrosis in Friedreich ataxia: a mitochondrial cardiomyopathy with metabolic syndrome

Cardiomyopathy produces significant mortality in patients with Friedreich ataxia (FA), a genetic disorder that produces intra-mitochondrial iron accumulation. We sought to test the hypothesis that abnormal myocardial perfusion reserve and fibrosis represent early manifestations of cardiomyopathy. Twenty-six patients with genetically proven FA ages 36 ± 12 years without cardiomyopathy and eight controls underwent cardiac magnetic resonance with adenosine. Precontrast imaging for myocardial iron estimation was performed. Myocardial perfusion reserve index (MPRI) was quantified using the normalized upslope of myocardial enhancement during vasodilator stress vs. rest. Left ventricular (LV) mass and volumes were computed from short-axis cine images. Serologies included lipids, and platelets were isolated for iron quantification using inductively coupled plasma mass spectrometry. Left ventricular ejection fraction and mass averaged 64.1 ± 8.3% and 62.7 ± 16.7 g/m², respectively, indicating preserved systolic function and absence of significant hypertrophy. Myocardial perfusion reserve index quantification revealed significantly lower endocardial-to-epicardial perfusion reserve in patients vs. controls (0.80 ± 0.18 vs. 1.22 ± 0.36, P = 0.01). Lower MPRI was predicted by increased number of metabolic syndrome (met-S) features (P < 0.01). Worse concentric remodelling occurred with increased GAA repeat length (r = 0.64, P < 0.001). Peripheral platelet iron measurement showed no distinction between patients and controls (5.4 ± 8.5 × 10⁻⁷ vs. 5.5 ± 2.9 × 10⁻⁷ ng/platelet, P = 0.88), nor did myocardial T2* measures. Patients with FA have abnormal myocardial perfusion reserve that parallels met-S severity. Impaired perfusion reserve and fibrosis occur in the absence of significant hypertrophy and prior to clinical heart failure, providing potential therapeutic targets for stage B cardiomyopathy in FA and related myocardial diseases.