Multifactorial determinants of reduced coronary flow reserve after dipyridamole in dilated cardiomyopathy

Coronary sinus blood flow (ml/100 g left ventricular [LV] mass/min) and coronary resistance (mean aortic minus LV mean diastolic pressures/coronary sinus blood flow, mm Hg/[ml/100 g/min]) were studied in 7 control patients and in 11 patients with severe dilated cardiomyopathy (DC) and normal coronary arteriograms. Basal coronary sinus blood flow was not different in the 2 groups. After intravenous administration of dipyridamole (0.14 mg/kg/min X 4 min), coronary sinus blood flow and dipyridamole/basal coronary sinus blood flow ratio were significantly (p less than 0.001) lower in the DC group than in the normal group (coronary sinus blood flow 188 +/- 48 vs 408 +/- 58, respectively; blood flow ratio 1.78 +/- 0.35 vs 4.01 +/- 0.56, respectively), and the coronary resistance was higher in the DC group than in the control group (0.39 +/- 0.15 vs 0.22 +/- 0.03, respectively, p less than 0.01). After administration of dipyridamole in patients with DC, no correlation could be found between coronary sinus blood flow and LV mean diastolic, mean aortic or coronary driving pressures, i.e., mean aortic minus LV mean diastolic pressures. Thus, in DC patients, neither an elevated LV diastolic pressure nor a low coronary perfusion pressure can totally account for the restriction of the coronary flow reserve after dipyridamole.     

Augmentation of myocardial blood flow in hypertensive heart disease by angiotensin antagonists: a comparison of lisinopril and losartan

OBJECTIVES: The goal of this study was to compare myocardial perfusion reserve (MPR) before and after long-term treatment with lisinopril and losartan in patients with hypertension and left ventricular hypertrophy (LVH). BACKGROUND: Studies have suggested that treatment with angiotensin-converting enzyme inhibitors (ACEIs) improves MPR in patients with hypertension by potentiating endogenous bradykinins. Because angiotensin receptor blockers (ARBs) lack a direct effect on bradykinins, we hypothesized that they may not improve MPR. METHODS: We measured pre- and post-treatment myocardial blood flow (MBF) by positron emission tomography in 17 patients (lisinopril: 9 patients, losartan: 8 patients) with hypertension and LVH at baseline and after coronary vasodilation with intravenous dipyridamole. In addition, we measured rest and hyperemic blood flow in eight normotensive controls. RESULTS: Post-treatment maximal coronary blood flow and MPR in the lisinopril group increased significantly compared with pretreatment values (3.5 +/- 1.2 vs. 2.6 +/- 1.1 ml/min/g, p = 0.02; 3.7 +/- 1.1 vs. 2.4 +/- 1 ml/min/g, respectively, p = 0.002, respectively). Post-treatment hyperemic flow in the patients treated with lisinopril was not significantly different from corresponding measurements in controls (3.5 +/- 1.2 vs. 3.9 +/- 1 ml/min/g, respectively, p = NS). In the patients treated with losartan, there was no difference between pre- and post-treatment MBF values and MPR. CONCLUSIONS: Myocardial perfusion reserve and maximal coronary flow improved in asymptomatic patients with hypertension-induced LVH after long-term treatment with lisinopril but not with losartan. Thus, ACEIs, but not ARBs, might be effective in repairing the coronary microangiopathy associated with hypertension-induced LVH.     

Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia

OBJECTIVE: The goal of this study was to examine the relationship between plasma asymmetric dimethylarginine (ADMA) level and hyperemic myocardial blood flow (MBF) in subjects with borderline hypertension (BHT) and familial hypercholesterolemia (FH). METHODS: Asymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase that may modulate vascular function.We measured plasma ADMA levels and myocardial flow in 77 young men (mean age 35 +/- 5 years), including 47 healthy controls, 16 men with BHT, and 14 men with FH. Basal and dipyridamole-induced myocardial flow was measured using positron emission tomography. Plasma ADMA levels were measured using high-pressure liquid chromatography. RESULTS: Asymmetric dimethylarginine levels were significantly elevated in the BHT group compared with controls (0.59 +/- 0.13 micromol/l vs. 0.43 +/- 0.12 micromol/l, p < 0.001), and they had significantly lower dipyridamole flow (2.85 +/- 1.20 ml/min/g vs. 3.69 +/- 1.68 ml/min/g, p < 0.05). In a multivariate regression model adjusted for the study group, dipyridamole flow was inversely associated with ADMA (p < 0.05), age (p < 0.05), and apolipoprotein B concentration (p < 0.05). CONCLUSIONS: We conclude that plasma ADMA concentration is related to dipyridamole-induced vasodilatory function in young men, independently of blood pressure elevation and hypercholesterolemia. Subjects with BHT have significantly increased plasma ADMA levels, which may partly explain the impaired hyperemic MBF in this condition.     

Catecholamines,Angiotensin II and Sodium Concentrations in Cerebrospinal Fluid in Young Men with Borderline Hypertension

To evaluate the role of central nervous mechanisms and their relationships to the peripheral sympathetic nervous system in borderline hypertension, we measured catecholamines, angiotensin II (AII) and sodium (Na) concentrations in cerebrospinal fluid (CSF) with plasma catecholamines concomitantly in 12 young men with borderline hypertension and 7 age-matched healthy normotensive men on ordinary salt intake. Plasma norepinephrine (NE) and epinephrine (E) were higher in the borderline hypertensives than in the normotensives (NE: 239 ± 15 vs 190 ± 11 pg/ml, p < 0.05, E: 83 ± 9 vs 43 ± 6 pg/ml, p < 0.01). NE levels in CSF were also higher in the borderline hypertensives than in the normotensives (200±15 vs 150 ± 18 pg/ml, p < 0.05). In most of the subjects, CSF E and plasma and CSF dopamine levels were below the sensitivity of the assay. CSF NE correlated positively with both plasma NE (p < 0.01) and mean blood pressure (p < 0.05) in all subjects. Immunoreactive All and Na concentrations in CSF did not differ between the borderline hypertensives and normotensives. These results suggest that peripheral sympathoadrenal overactivity in young subjects with borderline hypertension may be related to an altered function of central noradrenergic neurons. A11 and Na in the central nervous system do not appear to have an important role in borderline hypertension     

Comparison of myocardial blood flow during dobutamine-atropine infusion with that after dipyridamole administration in normal men

OBJECTIVES: The present study was designed to compare the absolute myocardial blood flow (MBF) after intravenous dipyridamole infusion with that during dobutamine-atropine administration in normal healthy male volunteers. BACKGROUND: Both safety and usefulness of dobutamine-atropine stress in myocardial perfusion imaging have been reported. However, no information exists on whether the magnitude ofhyperemia achieved with dipyridamole and dobutamine-atropine is comparable. METHODS: Myocardial blood flow was measured with positron emission tomography and 15O-labeled water in 20 healthy young men (23 +/- 3 years) 1) at baseline, 2) after dipyridamole infusion (0.56 mg/kg over 4 min), and 3) during dobutamine (40 microg/kg/min) and atropine (0.25 to 1.0 mg) infusion. RESULTS: The MBF was significantly increased during dipyridamole infusion and during dobutamine-atropine stress compared with at rest (4.33 +/- 1.23 and 5.89 +/- 1.58 vs. 0.67 +/- 0.16 ml/min/g, respectively, p < 0.0001). Moreover, dobutamine-atropine infusion produced greater MBF compared with dipyridamole (p = 0.0011), while coronary vascular resistance did not differ significantly after dipyridamole administration and during dobutamine-atropine infusion (17.6 +/- 7.9 vs. 18.6 +/- 5.6 mm Hg/[ml/min/g], respectively). CONCLUSIONS: Near maximal coronary vasodilatation caused by dipyridamole is attainable using dobutamine and atropine in young healthy volunteers. Dobutamine in conjunction with atropine is no less effective than dipyridamole in producing myocardial hyperemia.     

Coronary dilatory capacity in idiopathic dilated cardiomyopathy: Analysis of 16 patients

Hemodynamic function and overall coronary blood flow (argon technique) were measured in 16 patients with idiopathic dilated cardiomyopathy (IDC) and in 12 patients without detectable heart disease (control subjects) referred for precordial pain. In patients with IDC, coronary blood flow was normal at rest (78 ± 17 ml/100 g·min versus 78 ± 9 in control subjects). During maximal inducible coronary vasodilation (dipyridamole, 0.5 mg/kg), coronary blood flow was significantly reduced (142 ± 38 ml/100 g · min versus 301 ± 64 in control subjects; p < 0.001). Consequently, obtainable minimal coronary resistance was increased in IDC (0.54 ± 0.20 mm Hg/ml/100 g · min versus 0.23 ± 0.04 in control subjects; p < 0.001). In patients with IDC, left ventricular (LV) end-diastolic pressure was significantly increased (19 ± 11 mm Hg versus 6 ± 3 in control subjects; p < 0.005), and the LV ejection fraction was diminished (36 ± 11% versus 72 ± 3% in control subjects; p < 0.001). In patients with IDC, LV end-diastolic pressure correlated significantly with the obtained minimal coronary resistance after application of dipyridamole (r = 0.85; p < 0.001). LV catheter biopsy specimens revealed no alterations in myocardial microvasculature. Thus, coronary dilatory capacity is impaired in patients with IDC, due partially to an increase in extravascular component of coronary resistance.     

The effect of intravenous nitroglycerin on coronary blood flow and infarct size during myocardial infarction in conscious dogs

Nitroglycerin (TNG), based on electrocardiographic evidence, has been shown to reduce myocardial ischemia, but its effect on morphometrically and enzymatically estimated infarct size has not been defined. Accordingly, coronary occlusion was produced in 50 conscious dogs without LV failure. Twenty-five received TNG (200–300 m?g/min i.v. for 8 h) and the results compared with those in 25 untreated dogs. Coronary blood flow was measured with ¹⁴¹Ce, ⁸⁵Sr, and ⁹⁵Nb (9 m?m) after occlusion before TNG, 30 min after TNG, and again at 8 h. Mean blood pressure decreased from 103 to 84 mmHg with TNG vs. 99 to 94 mmHg in controls (p<0.02). Average heart rates were similar [135±26 vs. 120±33 beats/min (SD)]. TNG Did not increase total transmural coronary flow in any region but increased subendocardial flow in the central ischemic areas by 45% (0.09 ml/min/g vs. 0.13 ml/min/g). Animals were sacrificed after 24 h. Infarct size estimated morphometrically (25± 1.5 vs. 26± 1.5 of LV weight) and from myocardial CK depletion (23±2 vs. 23±2) was similar for the two groups. Thus, despite increased subendocardial flow, prolonged i.v. TNG did not decrease infarct size even though a difference of 15% would have been detected with this sample size. TNG May relieve coronary spasm but does not appear to be beneficial with sustained coronary occlusion.     

Structural cardiac changes in relation to 24-h ambulatory blood pressure levels in borderline hypertension

Abstract. Objectives. To investigate left ventricular hypertrophy (LVH) in relation to 24-h ambulatory blood pressure (24-ABPM) and insulin levels in borderline hypertension. Design. A case-control study. Subjects. Borderline hypertensive men (diastolic blood pressure (DBP) 85–94 mmHg, n = 69) and age-matched normotensive controls (DBP ≤ 80 mmHg. n = 69) from a population screening programme. Main outcome measures. Echocardiography (M-mode). insulin (RIA) and 24-APBM (Del Mar P-IV) levels. Results. The borderline group showed a significant increase in septal thickness (10.4±1.5 vs. 9.7±1.5 mm. P < 0.01), peak systolic wall stress (218±38 vs. 202±38 10³ dynes cm^?2, P < 0.05) and a decrease in LV ejection time (28.4±2.5 vs. 29.5±2.1s, P < 0.01). The septum vs. posterior wall thickness ratio was significantly higher in the borderline group (1.13±0.14 vs. 1.06±0.14, P < 0.01). Casual BP levels did not correlate with LVH indices, while 24-ABPM systolic levels correlated strongly with LVH indices in the borderline group (r = 0.22–0.52, P < 0.05) but not in the normotensive group. Insulin levels correlates strongly with LVH indices in the normotensive group (r = 0.34–0.47, P < 0.01) but not the borderline, group. Conclusions. Signs of asymmetric LVH and altered ventricular function are already detectable in borderline hypertension. The data also suggest that early structural cardiac changes are related to ambulatory blood pressure profile, but not to casual blood pressure or trophic factors such as insulin.     

Transmural myocardial blood flow distribution in hypertrophic cardiomyopathy and effect of treatment

Verapamil alleviates symptoms in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism of improvement remains speculative. Baseline and dipyridamole myocardial blood flow (MBF) were measured in 15 HCM patients (14 men, 42±10 years), before and after 4 weeks of verapamil SR 480 mg daily, using ¹⁵O labelled water and positron emission tomography (PET). Subendocardial (endo) and subpericardial (epi) MBF was measured in the septum (thickness 25.4±5.8 mm). Pre-treatment baseline whole heart MBF was 1.02±0.28 ml/min/g and 1.01±0.30 ml/min/g on treatment (p=ns). Dipyridamole MBF was 1.39±0.31 ml/min/g off treatment and 1.23±0.34 ml/min/g on treatment (p=ns). Coronary flow reserve (dipyridamole/resting MBF) was 1.45±0.52 and 1.30±0.51, respectively (p=ns). At baseline, the septal endo/epi MBF ratio was uniform off and on treatment (1.13±0.18 vs 1.18±0.21, p=ns). Before treatment, the endo/epi ratio following dipyridamole decreased to 0.93±0.24 (p<0.01 vs baseline) and 5/15 (33%) patients had a ratio <0.8 which would suggest subendocardial underperfusion. During treatment, the endo/epi ratio following dipyridamole was no more different from baseline (1.06±0.24, p=ns vs baseline) and 2/14 (14%) patients had an endo/epi <0.8. PET can be successfully used to determine transmural MBF in vivo in patients with hypertrophied ventricles. Despite symptomatic improvement, high dose verapamil therapy does not increase total MBF in patients with HCM but may improve septal transmural MBF distribution during dipyridamole in some patients. Received: 8 April 1998, Returned for revision: 6 May 1998, Revision received: 8 July 1998, Accepted: 2 September 1998     

Coronary flow reserve improves after aortic valve replacement for aortic stenosis: an adenosine transthoracic echocardiography study

OBJECTIVES: The goal of this study was to assess coronary flow reserve (CFR) before and after aortic valve replacement (AVR). BACKGROUND: Coronary flow reserve is impaired under conditions of left ventricular (LV) hypertrophy. It is not known whether CFR improves with regression of LV hypertrophy in humans. METHODS: We investigated 35 patients with pure aortic stenosis, LV hypertrophy and normal coronary arteriograms. Patients underwent adenosine transthoracic echocardiography on two occasions--immediately before AVR and six months postoperatively. Left ventricular mass, distal left anterior descending coronary artery (LAD) diameter, flow and CFR were assessed on each occasion. RESULTS: Distal LAD diameter was successfully imaged in 30 patients (86%), and blood flow was successfully imaged in 27 (77%). Paired data were subsequently available in 24 patients, of whom 14 were men, mean age 68.1+/-12.5 years, body mass index 24.5+/-2.0 kg/m2, aortic valve gradient 93+/-32 mm Hg. Pre- to post-AVR a significant decrease was seen in LV mass (271+/-38 vs. 236+/-32g, p<0.01) and LV mass index (154+/-21 vs. 134+/-21 g/m2, p< 0.01). Distal LAD diameter fell from 2.27+/-0.37 to 2.23+/-0.35 mm, p = 0.08). Pre- to post-AVR there was no significant change in resting parameters of peak diastolic velocity (0.43+/-0.16 vs. 0.41+/-0.11 m/s), distal LAD flow 23.3+/-10.1 vs. 20.9+/-5.2 ml/min or distal LAD flow scaled for LV mass (8.7+/-3.8 vs. 9.0+/-2.5 ml/min/100 g LV mass), but there was significant increase in hyperemic peak diastolic velocity (0.71+/-0.26 vs. 1.08+/-0.24 m/s; p<0.01), distal LAD flow (37.8+/-11.3 vs. 53.5+/-16.1 ml/min; p<0.01) and distal LAD flow scaled for LV mass (14.3+/-5.0 vs. 23.3+/-8.5 ml/min/100 g LV mass; p<0.01). Coronary flow reserve, therefore, increased from 1.76+/-0.5 to 2.61+/-0.7. CONCLUSIONS: Coronary flow reserve increases after AVR for aortic stenosis. This increase occurs in tandem with regression of LV hypertrophy.     

Dipyridamole vasodilator response after human orthotopic heart transplantation: quantification by oxygen-15-labeled water and positron emission tomography.

To assess coronary vasodilator reserve after orthotopic heart transplantation, regional myocardial perfusion was measured with oxygen-15-labeled water and dynamic positron emission tomography in 14 cardiac allograft recipients who were not experiencing rejection and who had no angiographic evidence of epicardial coronary sclerosis 15 to 73 months (mean +/- SD 43 +/- 19) after transplantation (group I). Twelve normal men with an average age of 31 years (group II) served as a control group. Regional perfusion was measured at rest and after the intravenous administration of 0.6 mg/kg body weight of dipyridamole. Rest regional myocardial blood flow was homogeneously distributed throughout the left ventricle and was significantly higher in transplant recipients (mean 1.16 +/- 0.26 ml/g per min [range 0.8 to 1.73] than in normal subjects (mean 0.85 +/- 0.13 ml/g per min [range 0.57 to 0.99]; p = 0.001) as was rest heart rate-systolic blood pressure product (rate-pressure product 11,255 +/- 2,540 vs. 7,073 +/- 1,306; p less than 0.001). After dipyridamole, perfusion in the transplant recipients was homogeneous and slightly lower (2.73 +/- 1.03 vs. 3.40 +/- 1.09 ml/g per min; p = NS), whereas rate-pressure product was slightly higher (12,179 +/- 2,266 vs. 10,885 +/- 1,895; p = NS) than the value in normal subjects. Dipyridamole vasodilator response (dipyridamole/rest myocardial blood flow) ranged from 1.23 to 4.92 (mean 2.50 +/- 1.13) in group I and from 2.65 to 5.45 (3.97 +/- 0.89) in group II (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular function in patients with coronary heart disease in the presence or absence of angina pectoris during exercise radionuclide ventriculography

This study compares left ventricular (LV) performance during exercise in patients with angiographically documented coronary artery disease (CAD) based on the presence or absence of angina pectoris during the index exercise tests. The patients were divided into 2 groups: Group I included 31 patients who had angina pectoris during the test and Group II included 43 who did not. Multivessel CAD was present in 21 patients (68%) in Group I and 26 patients (60%) in Group II (difference not significant [NS]). There were no significant differences between the 2 groups in age, sex, history of diabetes mellitus, history of myocardial infarction and in the exercise duration, work load, heart rate and systolic blood pressure. Exercise-induced ST-segment depression was present in 48% of the patients in Group I and in 40% in Group II (NS). The mean LV ejection fraction at rest was 52 ± 12% in Group I and 50 ± 17% in Group II (NS). There were significant differences in the 2 groups in the change from rest to exercise in ejection fraction (?4.5 ± 7.6% in Group I vs 1 ± 9.4% in Group II, p < 0.01), end-systolic volume (29 ± 38 ml in Group I vs 9 ± 23 ml in Group II, p < 0.005), the change in systolic blood pressure-to-end-systolic volume ratio (?0.1 ± 0.5 mm Hg/ml in Group I vs 0.3 ± 1.1 mm Hg/ml in Group II, p < 0.05), and wall motion score (?0.4 ± 0.6 in Group I vs 0.09 ± 0.7 in Group II, p < 0.05).Thus, asymptomatic myocardial ischemia may occur in patients with extensive CAD and be associated with abnormal exercise LV function; however, patients with symptomatic CAD have worse exercise LV function than those with asymptomatic CAD.     

右房左室起搏治疗慢性心力衰竭伴室内传导阻滞患者的初步临床观察

观察右房 左室起搏治疗慢性心力衰竭 (简称心衰 )的临床效果。选择 1 6例充血性心衰患者 (NYHA分级Ⅲ Ⅳ级 ) ,男 1 0例、女 6例 ,年龄 6 8.4± 6岁 ;均为窦性心律 ,合并有Ⅰ度房室阻滞 ,完全性左束支阻滞。按安置起搏器的模式分为右房 左室起搏治疗组 (LV组 ,n =6 ) ,右房双室起搏治疗组 (BiV组 ,n =1 0 )。左室起搏电极分别放置于心大静脉左室侧后分支 9例 ,心大静脉左室后分支 7例。观察起搏治疗前后左室心功能参数、6min步行距离、左室壁运动的同步性及体表心电图的变化。结果 :BiV组左室射血分数 (LVEF)由术前的 0 .2 3提高至 0 .31 (P <0 .0 0 1 ) ;在LV组LVEF由术前的 0 .2 4提高至 0 .33(P <0 .0 0 1 ) ;左室舒张末期容积指数在二组分别由术前的 1 4 9± 5 1ml/m2 和 1 5 3±5 3ml/m2 下降至 1 1 6± 38ml/m2 和 1 2 1± 4 1ml/m2 (P均 <0 .0 0 1 ) ;室间隔与左室后壁运动的延迟时间在二组分别由术前的 1 95± 94ms和 1 97± 89ms下降至 1 7± 6 0ms及 1 6± 5 6ms(P均 <0 .0 0 1 )。 6min步行距离则分别由术前的4 0 3± 5 3m和 4 0 1± 5 9m提高至 4 4 1± 6 2m和 4 4 2± 6 7m(P均 <0 .0 5 )。结论 :初步临床观察提示右房 左室起搏治疗与右房双室起搏治疗相比 ,同样可有效地改善慢性心衰?     

Acute coronary vascular and myocardial perfusion effects of conjugated equine estrogen in the anesthetized dog

Women generally exhibit angina rather than myocardial infarction as the first manifestation of heart disease. Postmenopausal use of hormone replacement therapy, specifically estrogens, is associated with reduced incidence of major cardiac events suggesting estrogen may protect the heart during ischemia. We recently showed that acute administration of conjugated equine estrogens prior to ischemia attenuated the ventricular arrhythmias of ischemia as well as those of reperfusion. This study looks at basal effects of estrogen on coronary blood flow and the effects of estrogen on regional blood flow during ischemia to determine if estrogen exerts its antiarrhythmic effects during ischemia by altering blood flow. Under conditions of natural blood flow, estrogen caused cyclic changes in blood flow. When coronary blood flow was controlled and limited, estrogen increased coronary perfusion pressure (118±8 mmHg vs. 85±10 mmHg in non-treated dogs, P<0.05) demonstrating an overall vasoconstrictor effect. Coronary blood flow and regional myocardial perfusion were determined before and during ischemia in anesthetized dogs with and without acutely-administered estrogen. Colored microspheres were injected at steady state prior to ischemia, and during steady state myocardial ischemia. Conjugated equine estrogen (10 μg/kg), administered about 6 min before ischemia, had no effect on regional perfusion under steady state conditions, nor in the non-ischemic zone during ischemia. Perfusion in the subepicardial and subendocardial ischemic zones in estrogen-treated dogs was significantly lower than in non-treated dogs [0.14±0.01 ml/min/g vs. 0.23±0.02 ml/min/g (P<0.05) in the epicardial ischemic zone; and, 0.15±0.02 ml/min/g vs. 0.22±0.03 ml/min/g (P<0.05) in the endocardial ischemic zone]. We conclude that the acute, systemic administration of estrogen in the anesthetized dog decreases regional perfusion in the ischemic myocardium and causes significant coronary vasoconstriction when flow is controlled and limited. Received: 3 March 1998, Returned for 1. revision: 28 April 1998, 1. Revision received: 29 May 1998, Accepted: 18 June 1998     

Relevance of coronary microvascular flow impairment to long-term remodeling and systolic dysfunction in hypertrophic cardiomyopathy.

OBJECTIVES: This study sought to evaluate whether the entity of microvascular dysfunction, assessed by positron emission tomography (PET), predicts the long-term development of left ventricular (LV) remodeling and systolic dysfunction in hypertrophic cardiomyopathy (HCM). BACKGROUND: A subgroup of patients with HCM developed LV dilation and systolic impairment. A causal role of coronary microvascular dysfunction has been suggested as the underlying pathophysiological mechanism. METHODS: Fifty-one patients (New York Heart Association functional class I to II) were followed up for 8.1 +/- 2.1 years after measurement of resting and dipyridamole (Dip) myocardial blood flow (MBF). Left ventricular systolic dysfunction was defined as an ejection fraction (LVEF) <50%. RESULTS: The Dip-MBF was blunted in HCM patients compared with a group of healthy control patients (1.50 +/- 0.69 ml/min/g vs. 2.71 +/- 0.94 ml/min/g; p < 0.001). At final evaluation, 11 patients (22%) had an LVEF <50%; in most (n = 7), systolic dysfunction was associated with a significant increase in LV cavity dimensions (>5 mm) during follow-up. These 11 patients showed lower Dip-MBF than the 40 with preserved LV function (1.04 +/- 0.38 ml/min/g vs. 1.63 +/- 0.71 ml/min/g, respectively; p = 0.001); Dip-MBF was particularly blunted in five patients with clinical progression to severe heart failure symptoms or death (Dip-MBF 0.89 +/- 0.15 ml/min/g). At multivariate analysis, the two independent predictors of systolic dysfunction were Dip-MBF in the lowest tertile (<1.1 ml/min/g; relative hazard, 7.5; p = 0.038) and an end-diastolic LV dimension in the highest tertile (>45 mm; relative hazard, 12.3; p = 0.031). CONCLUSIONS: Severe microvascular dysfunction is a potent long-term predictor of adverse LV remodeling and systolic dysfunction in HCM. Our findings indicate microvascular dysfunction as a potential target for prevention of disease progression and heart failure in HCM.     

Microvascular Dysfunction in Dilated Cardiomyopathy: A Quantitative Stress Perfusion Cardiovascular Magnetic Resonance Study

ObjectivesThis study sought to quantify myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) in dilated cardiomyopathy (DCM) and examine the relationship between myocardial perfusion and adverse left ventricular (LV) remodeling.BackgroundAlthough regarded as a nonischemic condition, DCM has been associated with microvascular dysfunction, which is postulated to play a role in its pathogenesis. However, the relationship of the resulting perfusion abnormalities to myocardial fibrosis and the degree of LV remodeling is unclear.MethodsA total of 65 patients and 35 healthy control subjects underwent adenosine (140 μg/kg/min) stress perfusion cardiovascular magnetic resonance with late gadolinium enhancement imaging. Stress and rest MBF and MPR were derived using a modified Fermi-constrained deconvolution algorithm.ResultsPatients had significantly higher global rest MBF compared with control subjects (1.73 ± 0.42 ml/g/min vs. 1.14 ± 0.42 ml/g/min; p < 0.001). In contrast, global stress MBF was significantly lower versus control subjects (3.07 ± 1.02 ml/g/min vs. 3.53 ± 0.79 ml/g/min; p = 0.02), resulting in impaired MPR in the DCM group (1.83 ± 0.58 vs. 3.50 ± 1.45; p < 0.001). Global stress MBF (2.70 ± 0.89 ml/g/min vs. 3.44 ± 1.03 ml/g/min; p = 0.017) and global MPR (1.67 ± 0.61 vs. 1.99 ± 0.50; p = 0.047) were significantly reduced in patients with DCM with LV ejection fraction ≤35% compared with those with LV ejection fraction >35%. Segments with fibrosis had lower rest MBF (mean difference: −0.12 ml/g/min; 95% confidence interval: −0.23 to −0.01 ml/g/min; p = 0.035) and lower stress MBF (mean difference: −0.15 ml/g/min; 95% confidence interval: −0.28 to −0.03 ml/g/min; p = 0.013).ConclusionsPatients with DCM exhibit microvascular dysfunction, the severity of which is associated with the degree of LV impairment. However, rest MBF is elevated rather than reduced in DCM. If microvascular dysfunction contributes to the pathogenesis of DCM, then the underlying mechanism is more likely to involve stress-induced repetitive stunning rather than chronic myocardial hypoperfusion.     

组织多普勒成像评价血压昼夜节律变异对左心室舒张功能的影响

目的探讨血压昼夜节律变异对左心室舒张功能的影响。方法31例非杓型高血压患者(非杓型组)和31例年龄、性别相匹配的杓型高血压患者(杓型组)入选。两组患者均行24 h动态血压监测和组织多普勒成像(DTI)检查。结果两组日间平均收缩压和平均舒张压无显著性差异,非杓型组的夜间平均收缩压和平均舒张压均显著高于杓型组[(145.1±34.5)mm Hg(1 mm Hg=0.133 kPa)vs(127.9±18.1)mm Hg,(94.2±38.1)mm Hgvs(78.5±18.2)mm Hg,P<0.05]。心脏超声检查显示两组在心腔内径、室壁厚度和左心室射血分数等参数无显著性差异,DTI结果显示非杓型组的平均组织舒张早期速度(MEa)、MEa/平均组织舒张晚期速度(MAa)显著低于杓型组[(5.9±2.1)cm/svs(7.8±3.1)cm/s,(0.68±0.56)cm/svs(0.95±0.39)cm/s,P<0.05和P<0.01)];非杓型组的MAa较杓型组明显升高[(9.5±2.8)cm/svs(8.6±1.7)cm/s,P<0.01]。结论血压昼夜节律变异可加重左心室舒张功能受损。对于存在血压昼夜节律变异的高血压患者应尽早诊断,积极治疗和加强随访。     

Impaired coronary vasodilatory capacity after dipyridamole administration in hypertrophic cardiomyopathy

To investigate mechanisms for a reduced coronary vasodilatory capacity in patients with hypertrophic cardiomyopathy (HCM), maximum coronary blood flow and minimum coronary vascular resistance were measured by administering dipyridamole (0.56 mg/kg) to 19 patients with non-obstructive HCM and to 7 control subjects. The maximum coronary blood flow was significantly lower (131 +/- 46 vs 192 +/- 41 ml/100 g . min, p less than 0.01, mean +/- SD) and the minimum coronary vascular resistance was significantly higher (0.64 +/- 0.23 vs 0.44 +/- 0.13 mmHg/ml/100 g . min, p less than 0.05) in HCM patients. There were no significant correlations between maximum coronary blood flow or minimum coronary vascular resistance and the baseline left ventricular end-diastolic pressure or the severity of systolic narrowing of the left anterior descending artery of the septal perforator. In contrast, the minimum coronary vascular resistance was correlated significantly with the left ventricular muscle mass (r = 0.55, p less than 0.05), but its correlation to small coronary vessel disease could not be studied. In addition, HCM patients with a reduced exercise tolerance (less than 7 metabolic units) demonstrated a significantly lower maximum coronary blood flow and higher minimum coronary vascular resistance than control subjects. These findings suggest that: (1) there is a group of HCM patients who have a reduced coronary vasodilatory capacity, (2) abnormal coronary vasculature is a possible underlining mechanism of HCM, either due to inadequate growth unassociated with left ventricular hypertrophy or as small coronary vessel disease, and (3) a reduced coronary vasodilatory capacity.     

Coronary Flow Reserve Is Impaired in Young Men With Familial Hypercholesterolemia

Objectives. We sought to investigate whether functional abnormalities in coronary vasomotion exist in young adults by studying 15 men (age 31 ± 8 years [mean ± SD]) with familial hypercholesterolemia (FH) and a matched group of 20 healthy control subjects.

Background. Precursors of morphologic coronary artery disease are known to be present in adolescents and young adults with a high risk factor profile.

Methods. Myocardial blood flow was measured at the basal state and during dipyridamole-induced hyperemia using positron emission tomography and oxygen-15–labeled water.

Results. Serum total and low density lipoprotein cholesterol concentrations were higher in the patients than in the control subjects (mean ± SD): 7.7 ± 1.9 versus 5.3 ± 1.5 mmol/liter (298 ± 73 vs. 205 ± 58 mg/dl) and 6.1 ± 1.8 versus 3.5 ± 1.4 mmol/liter (236 ± 70 vs. 135 ± 54 mg/dl), respectively (both p < 0.001). The baseline myocardial blood flow was similar in the patients and control subjects: 0.92 ± 0.24 versus 0.83 ± 0.13 ml/g per min, respectively (p = 0.21). A significant increase in flow was observed in both groups after dipyridamole infusion, but the flow at maximal vasodilation was 29% lower in the patients: 3.19 ± 1.59 versus 4.49 ± 1.27 ml/g per min (p = 0.011). Consequently, coronary flow reserve (the ratio of hyperemia flow to basal flow) was 35% lower in the patients than in the control subjects: 3.5 ± 1.6 versus 5.4 ± 1.5 (p = 0.0008). Total coronary resistance during hyperemia was higher in the patients than in the control subjects: 36 ± 25 versus 21 ± 10 mm Hg/min per g per ml (p = 0.045). Coronary flow reserve was inversely associated with serum total cholesterol concentration: r = −0.43 (p = 0.009).

Conclusions. Coronary flow reserve is reduced in young men with FH, and, consequently, coronary resistance during hyperemia is increased. The results demonstrate very early impairment of coronary vasomotion in hypercholesterolemic patients.

(J Am Coll Cardiol 1996;28:1705–11)     

Regional myocardial blood flow in man during dipyridamole coronary vasodilation

Regional myocardial blood flow before and after intravenous dipyridamole (0.56 mg/kg) was measured during cardiac catheterization in 11 patients using the 133Xe washout technique. Significant increases in heart rate (75 +/- 4 vs 87 +/- 6, p less than 0.004) and decreases in systolic blood pressure (144 +/- 8 vs 131 +/- 7, p less than 0.02) were observed with dipyridamole infusion. However, double product and cardiac output did not differ before or after drug infusion. Regional myocardial blood flow increased from 67 +/- 3 (SEM) to 117 +/- 3 ml/100 mg/min in myocardial segments supplied by nonobstructed coronary arteries. In stenotic coronary arteries, flow increased from 57 +/- 5 to 79 +/- 9 ml/100 mg/min with dipyridamole. We conclude that dipyridamole infusion results in flow differences which discriminate stenotic from nonstenotic coronary arteries.