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Biomedical subjects

M A Creager

Publications and source records attributed to M A Creager.

At least 91 records · Page 5Linked to original sources
PubMed1992

Baroreceptor reflex function in congestive heart failure.

Congestive heart failure is characterized by decreased parasympathetic and increased sympathetic nervous system activity. Impairment of baroreceptor reflex function may be relevant to this altered neural profile. The effect of cardiopulmonary and arterial baroreceptor stimulation on corresponding afferent neural activity is reduced in experimental models of heart failure. In addition, the heart rate and blood pressure responses to perturbations in arterial and carotid sinus pressure are less in animals with heart failure than in control animals. Comparable observations have been made in humans. Unloading cardiopulmonary baroreceptors with lower-body negative pressure causes less forearm vasoconstriction in patients with heart failure than in healthy subjects. The chronotropic response to changes in arterial and carotid sinus pressure induced by drug infusions or by use of a neck chamber is attenuated in heart failure. These data suggest that abnormalities in cardiopulmonary and arterial baroreceptor reflex function contribute importantly to altered autonomic nervous system activity in heart failure.

Animals↗
PubMed1992

Effect of isradipine on cardiopulmonary baroreflex function, regional blood flow, and vascular responsiveness in hypertensive patients.

Calcium channel antagonists, when used to treat hypertension, may modulate baroreflex function and vascular responsiveness to endogenous vasoconstrictors. We studied regional blood flow, cardiopulmonary baroreflex function, and pressor responses in nine hypertensive patients (mean age of 44 +/- 7 years), eight males and one female, treated with isradipine (ISR), a dihydropyridine calcium channel antagonist, in a placebo-controlled, crossover trial. Each patient underwent determination of blood pressure and forearm, splanchnic, and renal blood flows (by strain gauge plethysmography and indocyanine green and p-aminohippurate clearances, respectively) at baseline and during cardiopulmonary unloading by lower body negative pressure (LBNP) at -10 and -20 mm Hg. ISR decreased the mean arterial pressure from 105 +/- 2 to 93 +/- 2 mm Hg (p less than 0.01). ISR did not change supine forearm or splanchnic vascular resistances, but renal vascular resistance fell 30% during treatment (from 0.12 +/- 0.02 to 0.09 +/- 0.01 mm Hg min/ml, p less than 0.05). Cardiopulmonary baroreceptor unloading by LBNP elicited comparable effects on forearm, splanchnic, and renal vascular resistance before and during ISR treatment. Baroreceptor unloading during placebo did not change plasma NE or PRA; during ISR, LBNP elicited a progressive rise in these hormones. The pressor response to NE was potentiated during ISR treatment (p less than 0.05); in contrast, the pressor response to angiotensin II infusion was blunted by calcium blockade (p less than 0.05). The present study, therefore, demonstrates that calcium channel blockade with ISR preserves, and may even augment, cardiopulmonary baroreflex function. These physiologic responses may contribute to the relatively low incidence of symptomatic orthostatic hypotension observed during chronic treatment with this agent.

Adult↗
PubMed1992

L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans.

Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose of this study was to determine whether infusion of L-arginine, the precursor of the endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent vasodilation in hypercholesterolemic humans. Vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia (serum LDL cholesterol = 4.65 +/- 0.36 mmol/liter, P < 0.05). The vasodilative response to the endothelium-dependent vasodilator, methacholine chloride, was depressed in the hypercholesterolemic group, whereas endothelium-independent vasodilation, induced by nitroprusside, was similar in each group. Intravenous administration of L-arginine augmented the forearm blood flow response to methacholine in the hypercholesterolemic individuals, but not in the normal subjects. L-arginine did not alter the effect of nitroprusside in either group. D-arginine had no effect on forearm vascular reactivity in either group. It is concluded that endothelium-dependent vasodilation is impaired in hypercholesterolemic humans. This abnormality can be improved acutely by administration of L-arginine, possibly by increasing the synthesis of endothelium-derived relaxing factor.

Adult↗
PubMed1991

Prediction of major cardiac events after peripheral vascular surgery using dipyridamole echocardiography.

Patients undergoing peripheral vascular surgery are at increased risk of postoperative cardiac complications. To evaluate the role of dipyridamole echocardiography in predicting major cardiac events, 109 unselected patients undergoing elective peripheral vascular surgery were prospectively studied. Preoperative dipyridamole echocardiograms were interpreted by an echocardiographer unaware of all clinical data. Patients were followed up until hospital discharge by research physicians without knowledge of dipyridamole echocardiography results. Outcomes were classified using strict predefined criteria by reviewers unaware of other clinical and echocardiographic data. Of the 109 patients, 9 (8%) had positive studies defined as development of new regional wall motion abnormalities or worsening of preexistent wall motion abnormalities. Of these 9 patients, 7 had postoperative events, including 3 cardiac deaths, 1 nonfatal myocardial infarction, 2 with unstable angina, and 1 with pulmonary edema. Only 1 event occurred among the 100 patients with negative studies. The sensitivity and specificity of dipyridamole echocardiography for predicting cardiac events after vascular surgery were 88 and 98%, respectively; the positive and negative predictive values were 78 and 99%. The relative risk of having a cardiac event if dipyridamole echocardiography was abnormal was 78 (95% confidence interval, 11 to 564; p less than 0.0001). If these results are extended and confirmed by other investigators, preoperative dipyridamole echocardiography may be an important screening test for patients undergoing elective peripheral vascular surgery.

Aged↗
PubMed1991

Frequency of deep venous thrombosis in asymptomatic patients with coronary artery bypass grafts.

The frequency of deep vein thrombosis (DVT) in patients undergoing coronary artery bypass graft (CABG) surgery has not been established. Therefore to estimate the frequency of clinically silent DVT, we performed ultrasound examinations of the leg veins in 29 asymptomatic CABG patients before hospital discharge. We used high-resolution B-mode ultrasonography with color Doppler imaging. Fourteen (48.3%, 95% confidence interval 30.1 to 66.4%) had 20 documented leg vein thromboses, and all but one patient had DVT limited to the calf veins. Of the 20 thrombi 10 (50.0%) were present in the leg ipsilateral and 10 (50.0%) in the leg contralateral to the saphenous vein harvest site. None of the DVTs were suspected clinically. DVT was not associated with any local sign attributed to saphenous vein harvest such as pitting edema, incisional drainage, or local tenderness or with any putative risk factor for DVT such as cigarette use, distant history of malignancy, or varicose veins. Follow-up of these patients 5 to 11 months after CABG surgery showed no clinical evidence of DVT or pulmonary embolism. Our findings indicate that asymptomatic DVT of the calf occurs with surprisingly high frequency, 44.8% after CABG surgery. Future studies in patients undergoing CABG surgery should address the natural history of asymptomatic DVT, determine its clinical importance, and develop optimal strategies for prophylaxis and treatment.

Aged↗
PubMed1991

Arginine restores cholinergic relaxation of hypercholesterolemic rabbit thoracic aorta.

BACKGROUND: Reduced synthesis of endothelium-derived relaxing factor (EDRF) may explain impaired endothelium-dependent vasodilation in hypercholesterolemia. Accordingly, we designed studies to determine if endothelium-dependent relaxation in hypercholesterolemic rabbits may be restored by supplying L-arginine, the precursor of EDRF. METHODS AND RESULTS: Normal or hypercholesterolemic rabbits received intravenous L-arginine (10 mg/kg/min) or vehicle for 70 minutes. Subsequently, animals were killed, thoracic aortas were harvested, and vascular rings were studied in vitro. Rings were contracted by norepinephrine and relaxed by acetylcholine chloride or sodium nitroprusside. Vasorelaxation was quantified by determining the maximal response (expressed as percent relaxation of the contraction) and the ED50 (dose of drug inducing 50% relaxation; expressed as -log M). In vessels from hypercholesterolemic animals receiving vehicle, there was a fivefold rightward shift in sensitivity to acetylcholine compared with normal animals (p = 0.05, n = 5 in each group). In vessels from hypercholesterolemic animals, L-arginine augmented the maximal response to acetylcholine (83 +/- 16% versus 60 +/- 15%, p = 0.04 versus vehicle) and increased the sensitivity to acetylcholine (ED50 value: 6.7 +/- 0.2 versus 6.2 +/- 0.2, p less than 0.05 versus vehicle). Arginine did not affect maximal and EC50 responses to acetylcholine in vessels from normal animals. Arginine did not potentiate endothelium-independent responses in either group. CONCLUSIONS: We conclude that the endothelium-dependent relaxation is normalized in hypercholesterolemic rabbit thoracic aorta by in vivo exposure to L-arginine, the precursor for EDRF.

Animals↗
PubMed1991

Limb vascular responsiveness to beta-adrenergic receptor stimulation in patients with congestive heart failure.

BACKGROUND: In patients with congestive heart failure, the chronotropic and inotropic responses to beta-adrenergic agonists are reduced. It is not known whether desensitization of peripheral beta-adrenoceptors accounts for impaired limb vasodilation in these patients. Accordingly, we studied 14 normal subjects and 13 age-matched patients with congestive heart failure. METHODS AND RESULTS: To distinguish vasodilation mediated by beta-adrenoceptors and adenylate cyclase from that mediated by stimulation of guanylate cyclase, each subject received intrabrachial artery infusions of isoproterenol (1-100 ng/min) and sodium nitroprusside (0.3-10 micrograms/min), respectively. Forearm blood flow was determined by venous occlusion plethysmography. Maximal vasodilative potential, determined during reactive hyperemia, was reduced in the patients with congestive heart failure. The maximal forearm blood flow response to isoproterenol was comparable in patients with heart failure and in normal subjects (8.0 +/- 1.1 versus 9.2 +/- 1.2 ml/100 ml of tissue/min, respectively, p = NS). Furthermore, the dose-response relation to isoproterenol was similar in both groups. Likewise, the forearm vasodilative response to sodium nitroprusside was preserved in the heart failure group. Plasma concentration of norepinephrine was higher in the patients with heart failure (436 +/- 34 versus 201 +/- 74 pg/ml, p less than 0.01). When both groups were considered, there was no correlation between norepinephrine levels and the maximal forearm blood flow response to isoproterenol (r = 0.10, p = NS). CONCLUSIONS: We conclude that beta-adrenoceptor desensitization does not occur in the limb vessels of patients with congestive heart failure.

Adrenergic beta-Agonists↗
PubMed1991

Sodium depresses arterial baroreceptor reflex function in normotensive humans.

Sodium may contribute to the pathogenesis of hypertension by impairing arterial baroreceptor reflex function. The objectives of this study were to 1) determine whether a high sodium diet depresses arterial baroreceptor reflex function in normotensive humans, and 2) determine whether alterations in baroreceptor reflex function are related to changes in arterial compliance. Seventeen normotensive men, aged 30 +/- 2 years, received 10 and 200 meq sodium per day diets, each for 5 days, in a randomized crossover trial. Carotid baroreceptor reflex function was assessed by measuring the blood pressure response to sequential neck suction (0, -10, -20, and -30 mm Hg) and neck pressure (0, +10, +20, and +30 mm Hg). Forearm vascular resistance was determined by venous occlusion plethysmography. Arterial compliance was evaluated by calculating the quotient of the diastolic blood pressure decay time constant and forearm vascular resistance. Blood pressure averaged 124 +/- 3/62 +/- 2 mm Hg on the low sodium diet and 122 +/- 3/60 +/- 2 mm Hg on the high sodium diet (p = NS). Baroreceptor reflex slopes representing the systolic and diastolic blood pressure responses to changes in neck chamber pressure were steeper in the subjects when randomly assigned to low sodium diet than to high sodium diet. Diastolic blood pressure decay time and forearm arterial compliance were similar during low and high sodium intake. We conclude that short-term exposure to a high sodium diet depresses carotid baroreceptor reflex function in normotensive humans. This observation cannot be attributed to changes in the arterial compliance.

Adult↗
PubMed1991

Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis.

The purpose of this study was to assess the effect of atherosclerosis on the regulation of limb blood flow. To examine this issue, the reactivity of resistance and conduit vessels was evaluated in 11 patients with peripheral atherosclerotic disease and six control subjects. Responsiveness of resistance vessels was measured by venous occlusion plethysmography. Responsiveness of conduit vessels was determined by quantitative angiography to measure the diameter of the superficial femoral artery. To distinguish endothelium-dependent vasodilation from that caused by direct smooth muscle relaxation, each participant received intra-arterial infusions of methacholine and nitroprusside, respectively. Flow-mediated dilation of the superficial femoral artery was determined during reactive hyperemia. Vasoconstrictor function was determined by the infusion of phenylephrine. Methacholine reduced calf vascular resistance in the control subjects but not in the patients with atherosclerosis (-64 +/- 11% versus 6 +/- 18%, p less than 0.01). Nitroprusside decreased calf vascular resistance comparably in each group (-51 +/- 5% versus -42 +/- 4%, p = NS). The vasoconstrictor effect of phenylephrine was similar in each group (105 +/- 30% versus 108 +/- 22%, p = NS). In the superficial femoral artery, the vasodilator responses to both methacholine (20 +/- 4% versus 1 +/- 4%, p less than 0.05) and nitroprusside (19 +/- 4% versus 5 +/- 4%, p less than 0.05) were blunted in the atherosclerotic patients as was the vasoconstrictive response to phenylephrine (-15 +/- 1% versus -1 +/- 5%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1990

Long-term prognosis of myocardial ischemia detected by Holter monitoring in peripheral vascular disease.

To assess the long-term prognostic significance of myocardial ischemia, as measured by ambulatory electrocardiographic monitoring, in patients with occlusive peripheral arterial disease, 176 eligible patients scheduled for elective peripheral arterial surgery at Brigham and Women's Hospital were prospectively studied. All patients were monitored preoperatively without alterations to baseline medications. Prospective follow-up was obtained during routine medical care as provided by blinded, independent physicians and by subsequent telephone contact with the patients. Thirty-two patients (18%) had a total of 75 episodes of myocardial ischemia, 73 (97%) of which were asymptomatic. During a mean follow-up period of 615 days, there were 9 cardiac deaths, 1 occurring in-hospital after peripheral vascular surgery, and 13 nonfatal myocardial infarctions, 4 occurring in-hospital after peripheral vascular surgery. Cardiac events occurred in 12 of 32 patients with ischemia (38%), including 6 cardiac deaths, and in 10 of 144 patients without ischemia (7%), including 3 cardiac deaths (risk ratio 5.4, 95% confidence interval 2.6 to 11.4). The sensitivity of ischemia was 55%, the specificity was 87%, the positive predictive value was 38%, and the negative predictive value was 93%. In a multivariate Cox proportional-hazards model controlling for age, gender, coronary risk factors, history of angina, myocardial infarction, coronary artery disease and antianginal medications, the presence of ischemia was the only independent predictor of outcome. In patients with peripheral arterial disease, who often are unable to perform adequate exercise testing, ambulatory monitoring for myocardial ischemia is a significant independent predictor of 1- to 2-year prognosis.

Adult↗
PubMed1990

Nerve regeneration and reinnervation after limb amputation and replantation: clinical and physiological findings.

A 22-year-old male was studied 3 1/2-4 1/2 years after a traumatic section-avulsion amputation of the left upper extremity at the level of the distal humerus. The arm was reattached after a cold ischemia time of 4-5 hours and good vascularization was obtained. The ulnar nerve was repaired early with an end-to-end juncture while the median and radial nerves were repaired after seven months delay using a combination of vascularized radial nerve and nonvascularized sural nerve grafts. Some intrinsic hand muscle function had recovered. Pin-prick and touch sensation was present in all digits, although localization of touch stimulation was poor. Evoked motor responses had recovered by 25-50% of control amplitude in ulnar-innervated and by 10-25% in median-innervated muscles. Amplitudes of sensory responses from digit V had recovered by 25% and from digits I and III by 1-5%. Fast-adapting touch receptors had become reinnervated. There was electrophysiological evidence of aberrant sensory regeneration and of abnormal connections between sensory and motor fibers. Digital blood flow measurements suggested the presence of vascular obstruction in vessels of the replanted upper extremity. However, the digital vasoconstriction during cold exposure indicated regeneration of sympathetic nerve fibers.

Adult↗
PubMed1990

Baroreflex regulation of regional blood flow in congestive heart failure.

In patients with congestive heart failure (CHF), the distribution of the cardiac output is altered. Cardiopulmonary and arterial baroreceptors normally can regulate regional blood flow, but their contribution in heart failure is not known. To examine the role of baroreceptors in the regulation of regional blood flow in CHF, the effect of lower body negative pressure (LBNP) on forearm, renal, and splanchnic blood flow was evaluated in 12 patients with heart failure. Incremental LBNP at -10 and -40 mmHg decreased central venous pressure but had not effect on systolic blood pressure or pulse pressure. Renal blood flow decreased from 505 +/- 63 to 468 +/- 66 ml/min during LBNP -10 mmHg (P less than 0.05) and to 376 +/- 74 ml/min during LBNP -40 mmHg (P less than 0.01). Splanchnic blood flow decreased from 564 +/- 76 to 480 +/- 62 ml/min during LBNP -10 mmHg (P less than 0.01) and to 303 +/- 45 ml/min during LBNP -40 mmHg (P less than 0.01). Forearm blood flow did not decrease during LBNP -10 mmHg or -40 mmHg. To determine whether the absence of limb vasoconstriction during LBNP was confined to abnormalities in the baroreflex arc or was secondary to impaired end-organ responsiveness, six patients with heart failure and six normal subjects received an intrabrachial artery infusion of phenylephrine. Phenylephrine increased forearm vascular resistance comparably in each group. These data demonstrate that baroreceptors can regulate splanchnic and renal but not limb vascular resistance in patients with congestive heart failure and may contribute to the redistribution of blood flow that occurs in this disorder.

Aged↗
PubMed1990

Sex differences in control of cutaneous blood flow.

Women are far more likely than men to suffer from Raynaud's disease. The purpose of this study was to determine whether there are gender differences in local or central control of cutaneous blood flow that could account for the increased incidence of Raynaud's disease in women. To assess cutaneous blood flow, hand blood flow (HBF), finger blood flow (FBF), or skin perfusion (SP) was measured by fluid plethysmography, mercury strain-gauge plethysmography, or laser Doppler spectroscopy, respectively, in 47 volunteers. Basal HBF in men exceeded that of women (12.1 +/- 2.0 versus 6.2 +/- 1.5 ml/100 ml/min). Likewise, FBF in men surpassed that of women (19.5 +/- 4.1 versus 7.7 +/- 1.8 ml/100 ml/min). Similarly, SP in men was greater than that of women (270 +/- 42 versus 81 +/- 16 perfusion units). However, after total body warming (to induce a thermal sympatholysis), HBF in women exceeded that of men, suggesting that the lower basal HBF in women was due to increased sympathetic outflow to the extremities. Mental stress and deep inspiration reduced HBF and SP in men. Paradoxically, both of these maneuvers increased HBF and SP in women. To determine whether these paradoxical responses in women were due to the women's elevated basal sympathetic tone, these experiments were repeated after total body cooling in men to increase sympathetic tone and after total body warming in women to reduce sympathetic tone. Total body cooling reduced HBF and SP in men. Under these conditions, mental stress and deep inspiration induced vasodilation. In women, total body warming for 10 minutes increased HBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

L-arginine augments endothelium-dependent vasodilation in cholesterol-fed rabbits.

Evidence exists that an endothelium-derived relaxing factor is nitric oxide and that L-arginine is the precursor for the synthesis of nitric oxide in vitro. Whether exogenous L-arginine contributes to the modulation of vascular smooth muscle tone in vivo is still controversial. In hypercholesterolemia, resistance vessels do not relax normally in response to pharmacological stimuli that release endothelium-derived relaxing factor; bioassay experiments have suggested that impaired synthesis or release of endothelium-derived relaxing factor accounts, in part, for this blunted relaxation. We hypothesized that hypercholesterolemia reduces arginine metabolism and thereby impairs endothelium-derived relaxing factor synthesis. Accordingly, we designed a study to determine whether exogenous L-arginine could augment endothelium-dependent vasodilation of hind limb resistance vessels in anesthetized cholesterol-fed rabbits. Femoral blood flow was recorded with an electromagnetic flow probe in 16 cholesterol-fed and 12 control rabbits. The hind limb vasodilator responses to incremental intra-arterial infusions of acetylcholine (0.3-9.0 micrograms/kg/min) and nitroprusside (0.3-9.0 micrograms/kg/min) were studied before and during intravenous administration of L-arginine (10 mg/kg/min), D-arginine (10 mg/kg/min), or saline. The vasodilator response to acetylcholine was impaired in cholesterol-fed rabbits as compared with control rabbits. L-Arginine augmented vasodilation to acetylcholine in cholesterol-fed but not in control rabbits. L-Arginine did not alter the effect of nitroprusside in either group. Neither saline nor D-arginine changed the response to either acetylcholine or nitroprusside. Our data demonstrate that exogenous L-arginine normalizes the endothelium-dependent vasodilation of hind limb resistance vessels in cholesterol-fed rabbits.

Acetylcholine↗
PubMed1990

Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans.

The effect of hypercholesterolemia on vascular function was studied in humans. To eliminate the potential confounding effects of atherosclerosis, vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 111 +/- 7 mg/dl) and 13 patients with hypercholesterolemia (serum LDL cholesterol = 211 +/- 19 mg/dl, P less than 0.05). Each subject received intrabrachial artery infusions of methacholine, which releases endothelium-derived relaxant factor, and nitroprusside which directly stimulates guanylate cyclase in vascular smooth muscle. Maximal vasodilatory potential was determined during reactive hyperemia. Vasoconstrictive responsiveness was examined during intra-arterial phenylephrine infusion. Forearm blood flow was determined by venous occlusion plethysmography. Basal forearm blood flow in normal and hypercholesterolemic subjects was comparable. Similarly, reactive hyperemic blood flow did not differ between the two groups. In contrast, the maximal forearm blood flow response to methacholine in hypercholesterolemic subjects was less than that observed in normal subjects. In addition, the forearm blood flow response to nitroprusside was less in hypercholesterolemic subjects. There was no difference in the forearm vasoconstrictive response to phenylephrine in the two groups. Thus, the vasodilator responses to methacholine and nitroprusside were blunted in patients with hypercholesterolemia. We conclude that in humans with hypercholesterolemia, there is a decreased effect of nitrovasodilators, including endothelium-derived relaxing factor, on the vascular smooth muscle of resistance vessels.

Adult↗
PubMed1990

Pulsed and color Doppler analysis of normal carotid bifurcation flow dynamics using an in-vitro model.

An anatomically accurate model of the human carotid bifurcation was studied by using color Doppler flow mapping and pulsed Doppler signal analysis. In concordance with dye injection studies, a zone of flow separation was clearly demonstrated at the origin of the internal carotid artery opposite the flow divider. This zone of flow reversal was detected when the ratio of external to common carotid flow rates was greater than 0.27 and became progressively larger as the ratio increased, finally evolving into a zone of heterogenous flow at a ratio greater than 0.5. The authors conclude that the zone of flow reversal seen in the human carotid artery is a geometric property of the bifurcation and that its size depends on the relative flow between both branches. Doppler color imaging can be used to noninvasively map out its extent.

Blood Flow Velocity↗
PubMed1990

Early intervention in heart failure.

Treatment for patients with congestive heart failure is primarily directed at reducing symptoms and improving functional capacity. In patients with moderate to severe heart failure, therapeutic interventions incorporating diuretics, digoxin and selected vasodilators, specifically angiotensin-converting enzyme (ACE) inhibitors, are designed to correct pathophysiological mechanisms such as left ventricular dysfunction, excessive vasoconstriction and renal reabsorption of sodium and water. Physician-investigators are turning their attention to identifying and treating patients early in the course of their disease. Vasodilator therapy in patients with mild symptoms of heart failure may not only improve exercise performance, but also reduce mortality. In addition, recent studies have suggested that ACE inhibitors may prevent progression of disease in patients with asymptomatic left ventricular dysfunction. It is hoped that ongoing research will demonstrate that early identification and treatment of these patients may prevent development of symptoms and improve survival.

Heart Failure↗