A second locus for Marfan syndrome maps to chromosome 3p24.2-p25.

Marfan syndrome (MFS) is an autosomal dominant connective-tissue disorder characterized by skeletal, ocular and cardiovascular defects of highly variable expressivity. The diagnosis relies solely on clinical criteria requiring anomalies in at least two systems. By excluding the chromosome 15 disease locus, fibrillin 1 (FBN1), in a large French family with typical cardiovascular and skeletal anomalies, we raised the issue of genetic heterogeneity in MFS and the implication of a second locus (MFS2). Linkage analyses, performed in this family, have localized MFS2 to a region of 9 centiMorgans between D3S1293 and D3S1283, at 3p24.2-p25. In this region, the highest lod score was found with D3S2336, of 4.89 (theta = 0.05). By LINKMAP analyses, the most probable position for the second locus in MFS was at D3S2335.

The new Ghent criteria for Marfan syndrome: what do they change?

The diagnosis of Marfan syndrome (MFS) is challenging and international criteria have been proposed. The 1996 Ghent criteria were adopted worldwide, but new diagnostic criteria for MFS were released in 2010, giving more weight to aortic root aneurysm and ectopia lentis. We aimed to compare the diagnosis reached by applying this new nosology vs the Ghent nosology in a well-known series of 1009 probands defined by the presence of an FBN1 mutation. A total of 842 patients could be classified as MFS according to the new nosology (83%) as compared to 894 (89%) according to the 1996 Ghent criteria. The remaining 17% would be classified as ectopia lentis syndrome (ELS), mitral valve prolapse syndrome or mitral valve, aorta, skeleton and skin (MASS) syndrome, or potential MFS in patients aged less than 20 years. Taking into account the median age at last follow-up (29 years), the possibility has to be considered that these patients would go on to develop classic MFS with time. Although the number of patients for a given diagnosis differed only slightly, the new nosology led to a different diagnosis in 15% of cases. Indeed, 10% of MFS patients were reclassified as ELS or MASS in the absence of aortic dilatation; conversely, 5% were reclassified as MFS in the presence of aortic dilatation. The nosology is easier to apply because the systemic score is helpful to reach the diagnosis of MFS only in a minority of patients. Diagnostic criteria should be a flexible and dynamic tool so that reclassification of patients with alternative diagnosis is possible, requiring regular clinical and aortic follow-up.

What do French patients and geneticists think about prenatal and preimplantation diagnoses in Marfan syndrome?

OBJECTIVES: Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with manifestations mainly involving the skeletal, ocular, and cardiovascular systems. The phenotypic variability observed in MFS makes genetic counselling difficult. Prenatal diagnosis (PND) and preimplantation genetic diagnosis are technically feasible when a causal mutation is identified, but both raise many ethical questions in this condition. Little is known about opinions and practices in such reproductive issues in MFS. The goal of this study was to report on patients' points of view and geneticists' standard practices. METHODS: Two different questionnaires were produced. RESULTS: Fifty geneticists filled in the questionnaire. Twenty-two per cent thought that PND was acceptable, 72% debatable and 6% not acceptable. Preimplantation genetic diagnosis was more often reported acceptable (34% of answers). Results varied according to the physician's experience with the disease. Fifty-four answers were collected for patients' questionnaires. Most of them (74%) were favourable to the development of prenatal testing, and believed that the choice should be given to parents. However, only a minority would opt for prenatal diagnosis for themselves. CONCLUSION: This study showed that the majority of patients were in favour of PND and that opinions among practitioners varied widely, but that overall, practitioners favoured a systematic multidisciplinary evaluation of the couple's request.

Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for Marfan syndrome: further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion.

Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes. A proportion of patients carrying a FBN1 mutation does not meet diagnostic criteria for MFS, and are diagnosed with "other type I fibrillinopathy." In order to better describe this entity, we analyzed a subgroup of 146 out of 689 adult propositi with incomplete "clinical" international criteria (Ghent nosology) from a large collaborative international study including 1,009 propositi with a pathogenic FBN1 mutation. We focused on patients with only one major clinical criterion, [including isolated ectopia lentis (EL; 12 patients), isolated ascending aortic dilatation (17 patients), and isolated major skeletal manifestations (1 patient)] or with no major criterion but only minor criteria in 1 or more organ systems (16 patients). At least one component of the Ghent nosology, insufficient alone to make a minor criterion, was found in the majority of patients with isolated ascending aortic dilatation and isolated EL. In patients with isolated EL, missense mutations involving a cysteine were predominant, mutations in exons 24-32 were underrepresented, and no mutations leading to a premature truncation were found. Studies of recurrent mutations and affected family members of propositi with only one major clinical criterion argue for a clinical continuum between such phenotypes and classical MFS. Using strict definitions, we conclude that patients with FBN1 mutation and only one major clinical criterion or with only minor clinical criteria of one or more organ system do exist but represent only 5% of the adult cohort.

Contribution of molecular analyses in diagnosing Marfan syndrome and type I fibrillinopathies: an international study of 1009 probands.

BACKGROUND: The diagnosis of Marfan syndrome (MFS) is usually initially based on clinical criteria according to the number of major and minor systems affected following international nosology. The number of FBN1 mutation carriers, at risk of aortic complications who would not be properly diagnosed based only on clinical grounds, is of growing importance owing to the increased availability of molecular screening. The aim of the study was to identify patients who should be considered for FBN1 mutation screening. METHODS: Our international series included 1009 probands with a known FBN1 mutation. Patients were classified as either fulfilling or not fulfilling "clinical" criteria. In patients with unfulfilled "clinical" criteria, we evaluated the percentage of additional patients who became positive for international criteria when the FBN1 mutation was considered. The aortic risk was evaluated and compared in patients fulfilling or not fulfilling the "clinical" international criteria. RESULTS: Diagnosis of MFS was possible on clinical grounds in 79% of the adults, whereas 90% fulfilled the international criteria when including the FBN1 mutation. Corresponding figures for children were 56% and 85%, respectively. Aortic dilatation occurred later in adults with unfulfilled "clinical criteria" when compared to the Marfan syndrome group (44% vs 73% at 40 years, p<0.001), but the lifelong risk for ascending aortic dissection or surgery was not significantly different in both groups. CONCLUSIONS: Because of its implications for aortic follow-up, FBN1 molecular analysis is recommended in newly suspected MFS when two systems are involved with at least one major system affected. This is of utmost importance in patients without aortic dilatation and in children.

[NT-proBNP in practice: from chemistry to medicine]. / NT-proBNP en pratique "de la biologie à la clinique".

Since introduction of routine assay for natriuretic peptides, there are a growing number of clinical applications for those new tests. Numerous studies have defined analytical characteristics and clinical interest of NT-proBNP assay. Originally limited to acute heart failure diagnosis in the emergency room, NT-proBNP assay has now a wide number of applications. This review presents the "state of art" of this marker, detailing NT-proBNP physiological recent knowledge and its recognized or investigated clinical applications.

High prevalence of ventricular repolarization abnormalities in people carrying TGFßR2 mutations.

Mutations in the TGFßR2 gene have been associated with a life threatening risk of aortic dissection but no arrhythmic death has been previously reported. Two young females carrying a TGFßR2 mutation, initially diagnosed as Marfan syndrome or Loeys Dietz syndrome, presented sudden death with autopsy ruling out dissection. The ECGs of the 2 Sudden Cardiac Deaths revealed profound ventricular repolarization abnormalities with a sinusoidal T-U morphology associated with normal left ventricular ejection fraction. These data strongly suggest sudden cardiac arrhythmic deaths and prompted us to systematically study the repolarization pattern in the patients with TGFßR2 mutations. ECG findings from 58 mutation carriers patients (TGFßR2 group) were compared with those of 46 non-affected first degree relatives (control group). TGFßR2 mutation was associated with ventricular repolarization abnormalities in 47% of patients (p < 0.001 vs. controls), including a 19.6 ms (95%CI 8.7; 30.5) QTc interval prolongation compared to the non-affected first degree relatives (p < 0.001), higher prevalence of abnormal U waves (16% vs. 2%), and sinusoidal T-U morphology (10% vs. 0%). TGFßR2 mutations can be associated with abnormal ventricular repolarization pattern, longer QT interval than non-carrier relatives and an increased risk for sudden death.

Is the gap between guidelines and clinical practice in heart failure treatment being filled? Insights from the IMPACT RECO survey.

BACKGROUND: Recent registries have shown that recommended drugs for the treatment of chronic heart failure (CHF) are under-prescribed in daily practice. AIMS: To determine prescription rates of CHF drugs, and to assess predictive factors for drug prescription using data from a large panel of French cardiologists. METHODS AND RESULTS: We included 1919 outpatients, with NYHA class II-IV heart failure and a left ventricular ejection fraction <40%. The most frequently prescribed drugs were diuretics (83%), angiotensin converting enzyme inhibitors (ACE-I) (71%), beta-blockers (65%), spironolactone (35%) and angiotensin receptor blockers (ARB) (21%); 61% of patients received a combination of a beta-blocker and an ACE-I or ARB. Target doses were reached in 49% of the patients for ACE-I, but in only 18% for beta-blockers and in 9% for ARBs. Multivariate analyses showed that age >75 years was an independent factor associated with under-prescription of ACE-I-ARBs, beta-blockers or spironolactone. Renal failure was associated with a lower prescription of ACE-I-ARB and spironolactone, and asthma was a predictor of under-prescription of beta-blockers. CONCLUSIONS: In this contemporary survey, prescription rates of CHF drugs were higher than previously reported. However, dosages were lower than those recommended in guidelines. Age remained an independent predictor of under-prescription of CHF drugs.

[The best of cardiac failure in 2006]. / L'essentiel de 2006 en insuffisance cardiaque.

This year, several studies performed were justified by the increasing importance of diastolic dysfunction, while the systolic dysfunction remains stable. Its prognosis, previously considered as benign, is similar to heart failure due to systolic dysfunction. Studies are difficult in this field and we are often satisfied by imperfect results: PEP CHF, limited by the enrollment issue, showed only a trend for a beneficial effect of ACE-inhibitors. However the study can be considered as significant if only limited to the first year of follow-up, which can be justified. The second major field of research is resynchronization therapy: echocardiographic studies keep on providing asynchrony criteria. The benefit is greater in case of less extended fibrosis, and if the heart disease is non-ischemic, and if the paced zone does not contain fibrosis. Finally, a promising study on the interest of left ventricular discharge by a long-term circulatory assistance in case of severe systolic dysfunction should be cited.

Eclipsed mitral regurgitation: an unusual cause of acute heart failure.

AIMS: So far, a total of five patients with eclipsed mitral regurgitation (MR) have been reported in the literature by three different teams. The aim of this article was to detail clinical and echocardiographic characteristics, and outcome of patients presenting eclipsed MR. METHODS AND RESULTS: We defined eclipsed MR as spontaneous appearance, at rest, from 1 min to the next of an acute restriction in the motion of mitral leaflets preventing coaptation and leading to massive MR in patients with normal left ventricular end-diastolic diameter, left ventricular ejection fraction >45%, and baseline MR ≤2. Spontaneous regression occurred within 30 min, and no obvious trigger such as acute hypertension, new-onset arrhythmia, or myocardial ischaemia is present. Clinical data, ECG, echocardiographic data, surgery report, and follow-up status of six patients with eclipsed MR are reported: all were post-menopausal women with median age of 74 [57-80] years presenting hypertension (4/6), chronic kidney disease (5/6), or chronic anaemia (4/6). Five out of six patients experienced acute pulmonary oedema requiring hospitalization and underwent mitral valve replacement because of heart failure recurrence. Two patients died in the first days after surgery while the three others are free of symptoms at, respectively, 56, 18, and 10 months follow-up. CONCLUSION: Eclipsed MR is a clinical and echocardiographic syndrome responsible for heart failure with preserved EF. It is presently underdiagnosed and should be evoked in cases of recurrent acute pulmonary oedema without obvious trigger, in particular in patients presenting discordant evaluation of MR severity over time.

Management of heart failure in the elderly: recommendations from the French Society of Cardiology (SFC) and the French Society of Gerontology and Geriatrics (SFGG).

Heart failure, a frequent disease in the elderly, has a pejorative prognosis. Clinical diagnosis is complicated by atypical or difficult-to-interpret symptoms and by the concomitant presence of other diseases, particularly cognitive impairment, neurological disorders and diseases of the musculoskeletal system. Among the additional investigations, echocardiography remains underused. Impairment of diastolic left ventricular function is frequent. The usual laboratory tests must include calculation of the creatinine clearance, which is indispensable for dosage adjustment of certain drugs (ACE inhibitors, digoxin, spironolactone). The value of plasma natriuretic peptide assays as diagnostic tools has not been determined in elderly or very elderly populations and the plasma B-type natriuretic peptide increases with age. Comprehensive geriatric assessment is essential in order to screen for concomitant diseases and determine the patient's degree of dependence. The general objectives of treatment remain applicable to the elderly subject: improvement in the quality of life, reduction of mortality and the number and duration of hospitalisations, and slowing disease progression. In the frail elderly subject, symptom alleviation is to be the primary objective. In the absence of specific studies on elderly or very elderly subjects, most of the recommendations have been extrapolated from the data based on the evidence generated in younger populations. The dietary rules are to be more flexible than those used for younger subjects, particularly in order to prevent the risk of denutrition induced by strict salt-free diets. Special precautions for the use of heart failure drugs are due to comorbidities and the pharmacokinetic and pharmacodynamic changes related to aging. Drugs dosage increase is to be cautious and carefully monitored for adverse reactions. The therapeutic programmes in which multidisciplinary teams are involved reduce the number and duration of hospitalisations and the costs generated by the disease.

[The best of cardiac failure in 2005]. / L'essentiel de 2005 en insuffisance cardiaque.

The year 2005 saw the validation of resynchronisation treatment of cardiac failure with improved mortality in certain symptomatic patients under optimal medical therapy with QRS duration >150 msec. The implantable defibrillator has ousted the last antiarrhythmic drug, amiodarone, on which hopes for a reduction in mortality had been based. The positive inotropic agents have thrown their last reserves into the fight against cardiac failure: the anti-endothelins have not yet been shown to have significant benefits. The year 2005 was also the year of recommendations: European in acute and chronic heart failure, and American. The importance of clinical practice has been emphasised by the role given to registers. Finally, the diseases change: cardiomyopathy of stress is recognised in this stressful era; the importance of polypathology is increasingly understood in the elderly; the importance of renal function has been underlined although the method of its evaluation is less clear. As usual, there have been many advances in 2005, difficult to summarise in just a few lines.

[Medical management of Marfan's syndrome and ascending aortic aneurysms in France: initial assessment]. / Prise en charge médicale du syndrome de Marfan et des anévrismes de l'aorte ascendante en France: un premier bilan.

Over the last 30 years, there has been considerable progress in the management of aneurysms of the ascending aorta whether isolated or related to Marfan's syndrome which has considerably increased the life expectancy of these patients. The aim of this study was to assess the management protocol proposed in France for this condition in order to establish recommendations. A questionnaire was sent to cardiologists, paediatric cardiologists and cardiac surgeons and also to patients diagnosed with Marfan's syndrome. Most of the 228 physicians who replied prohibited violent sporting activities and less than a quarter advised against all sports. There was a wide dispersion in the prescription of beta blockers in Marfan's syndrome as 57% proposed this treatment only in cases with dilatation of the aorta and 5% prescribed no treatment at all. On the other hand, beta blockers were widely prescribed (93%) after replacement of the ascending aorta. When poorly tolerated in adults, the most commonly prescribed option was a calcium antagonist (60%) followed by angiotensin converting enzyme inhibitors and therapeutic abstention. On the other hand, 60% of paediatric cardiologists preferred to withdraw treatment. These results were confirmed by the replies from patients with Marfan's syndrome: 58.3% were prescribed beta blockers with a higher proportion in children less than 12 years of age. This treatment was introduced late, about 7 years after diagnosis. The authors conclude that there is much disparity in the management of ascending aortic aneurysms whether or not associated with Marfan's syndrome, especially with regards the prescription of beta blockers, justifying the publication of recommendations.

[Type B natriuretic peptide (BNP) versus n-terminal type B natriuretic propeptide in the diagnosis of cardiac failure in the elderly over 75 population]. / Peptide natriurétique de type B (BNP) versus n-terminal propeptide natriurétique de type B (NT-proBNP) pour le diagnostic de l'insuffisance cardiaque chez le sujet agé de plus de 75 ans.

Type B natriuretic peptide (BNP) versus n-terminal type B natriuretic propeptide in the diagnosis of cardiac failure in the elderly over 75 population The value of BNP is well established in the diagnosis of cardiac failure in cases of dyspnoea in the emergency room in young and, more and more, in elderly subjects. However, there are few studies comparing the diagnostic value of BNP and of the n-terminal pro-BNP in patients over 75 years of age. The aim of this study was to compare the diagnostic value of BNP and NT-pro BNP in dyspnoea of the elderly patient. One hundred and three consecutive patients over 75 years of age admitted to the emergency unit for dyspnoea were included. A blood sample for measuring the BNP (Biosite) and the NT-proBNP (Roche Diagnostic) was taken in the admission unit in addition to the standard blood workup. The final reference diagnosis was established by two independent cardiologists. Of the 103 patients, 61 were women and the average age was 84.9 +/- 6.2 years. The final diagnosis was cardiac failure in 49 patients (48%), pulmonary embolism in 6 patients, an acute exacerbation of chronic obstructive airways disease in 36 patients and an acute bronchitis in 30 patients. In 9 cases, the dyspnoea was considered to result from mixed cardiac and pulmonary disease. Renal function was assessed by calculating the creatinine clearance by Cockcroft and Gault's formula. The average value of the creatinine clearance was 41.7 +/- 16.4 ml/min indicating that mild renal failure was relatively common. The diagnostic value, assessed by the area under the ROC curve, was similar for the BNP (0.79; CI: 0.70-0.88) and NT-proBNP (0.80; CI: 0.71-0.89). A BNP value of 300 pg/ml had the same sensitivity and specificity as an NT-proBNP of less than 1 500 pg/ml. A BNP of less than 200 pg/ml and an NT-proBNP of less than 1 000 pg/ml had excellent negative predictive values for excluding the diagnosis of cardiac failure. The authors conclude that the BNP and NT-proBNP are useful for the diagnosis of cardiac failure in acute dyspnoea of the elderly and seem to have a comparable diagnostic value.

Central pulse pressure is a major determinant of ascending aorta dilation in Marfan syndrome.

BACKGROUND: In patients with Marfan syndrome (MFS), brachial pulse pressure (PP) has been recognized as a risk factor for aortic dilatation, leading to aortic dissection, the main cause of premature death. However, the relationships between aortic PP, aortic stiffness, and aortic root dilation have not been investigated. Our main objective was to determine whether central PP, which takes into account wave reflections and aortic stiffness, is a better determinant of ascending aorta diameter than brachial PP in MFS patients. METHODS AND RESULTS: Twenty patients with confirmed MFS and 20 age- and sex-matched control subjects were included in this cross-sectional, noninvasive study. Elastic properties of the abdominal aorta and common carotid, common femoral, and radial arteries were calculated from the pulsatile changes in arterial diameter and pressure. The ascending aorta diameter, measured with conventional echocardiography, was 37% larger in MFS than in control subjects (P<0.001). Arterial distensibility was 38% lower in MFS than in control subjects at the site of the abdominal aorta (P<0.01) but not at other sites (common carotid, common femoral, and radial arteries). Independently of age and body surface area, ascending aorta diameter was positively correlated with carotid PP in MFS (P<0. 01) and negatively in control subjects (P<0.01) but was not correlated with brachial PP and mean blood pressure. CONCLUSIONS: In patients with MFS, local PP, estimated from carotid PP, was a major determinant of ascending aorta diameter, whereas brachial PP was not. Increased arterial stiffness was confined to the aorta.

Addition of angiotensin II receptor blockade to maximal angiotensin-converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure.

BACKGROUND: Incomplete suppression of the renin-angiotensin system during long-term ACE inhibition may contribute to symptomatic deterioration in patients with severe congestive heart failure (CHF). Combined angiotensin II type I (AT1) receptor blockade and ACE inhibition more completely suppresses the activated renin-angiotensin system than either intervention alone in sodium-depleted normal individuals. Whether AT1 receptor blockade with losartan improves exercise capacity in patients with severe CHF already treated with ACE inhibitors is unknown. METHODS AND RESULTS: Thirty-three patients with severe CHF despite treatment with maximally recommended or tolerated doses of ACE inhibitors were randomized 1:1 to receive 50 mg/d losartan or placebo for 6 months in addition to standard therapy in a multicenter, double-blind trial. Peak aerobic capacity (V(O2)) during symptom-limited treadmill exercise and NYHA functional class were determined at baseline and after 3 and 6 months of double-blind therapy. Peak V(O2) at baseline and after 3 and 6 months were 13.5+/-0.6, 15.1+/-1.0, and 15.7+/-1.1 mL. kg-1. min-1, respectively, in patients receiving losartan and 14.1+/-0.6, 14.3+/-0.9, and 13.6+/-1.1 mL. kg-1. min-1, respectively, in patients receiving placebo (P<0.02 for treatment group-by-time interaction). Functional class improved by at least one NYHA class in 9 of 16 patients receiving losartan and 1 of 17 patients receiving placebo. CONCLUSIONS: Losartan enhances peak exercise capacity and alleviates symptoms in patients with CHF who are severely symptomatic despite treatment with maximally recommended or tolerated doses of ACE inhibitors.

Reciprocal strains in the normal and ischemic myocardium and their relation to the size of the ischemic region.

Previous studies have reported "bulging" of the ischemic zone and reciprocal shortening of the normal zone during the isovolumetric contraction period. This study examines the interaction and relation of these reciprocal strains during the isovolumetric contraction period. Normal zone and ischemic zone segment length data were acquired at 1 ms intervals during acute ischemia in 10 open chest dogs. The relation of ischemic zone and normal zone segment length was inversely linear in the isovolumetric contraction period during steady state ischemia and during preload reduction (mean correlation coefficient 0.92). The slope derived from the regression analysis was the same as that determined from the first and last data points of the isovolumetric contraction period (correlation coefficient between the regression versus two-point slope 0.96). This slope was used to calculate the size of the ischemic area based on the hypothesis that the isovolumetric normal zone shortening quantitatively accounted for the ischemic zone bulging during the isovolumetric contraction period, with the percent risk region serving as a weighing factor. The calculated risk region correlated with the anatomic risk region (r = 0.83, p less than 0.01; n = 9) and was independent of preload. During the isovolumetric contraction period, left ventricular short-axis diameter shortened approximately 0.2%; 80% of the ischemic zone lengthening occurred during this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic cardiomyoplasty: effect of discontinuing latissimus dorsi muscle stimulation on left ventricular systolic and diastolic performance and exercise capacity.

OBJECTIVES: This study sought to assess the short-term effect of discontinuing latissimus dorsi muscle stimulation on left ventricular systolic and diastolic performance and exercise tolerance in patients with improved functional status by cardiomyoplasty, in whom latissimus dorsi muscle was fully conditioned. BACKGROUND: Cardiomyoplasty has consistently improved the functional status of patients, but the short-term effect of latissimus dorsi muscle contraction has not been assessed in these patients. METHODS: Right-heart catheterization, Doppler-echocardiography and maximal exercise testing with expired gas analysis were performed in 10 patients with congestive heart failure who had undergone cardiomyoplasty at least 6 months earlier. Data were obtained when the latissimus dorsi muscle was stimulated every other systole and after stimulation was discontinued for 1 h. The power of this study to detect a 10% difference was > 80%. RESULTS: After cardiomyoplasty, left ventricular ejection fraction increased from 0.22 +/- 0.08 (mean +/- SD) to 0.27 +/- 0.07 after 6 months (p < 0.02 vs. before cardiomyoplasty) and to 0.24 +/- 0.09 after 1 year; functional class went from 3.0 +/- 0.0 to 2.0 +/- 0.5 after 6 months and to 2.0 +/- 0.7 after 1 year (both p < 0.001 vs. before cardiomyoplasty). After discontinuation of latissimus dorsi muscle stimulation, cardiac index did not change (2.28 +/- 0.45 vs. 2.30 +/- 0.46 liters/min per m2). Mean systemic arterial and pulmonary capillary wedge pressures were also similar (85.2 +/- 6.0 vs. 88.4 +/- 5.6 mm Hg and 14.9 +/- 7.1 vs. 13.6 +/- 6.8 mm Hg, respectively). Doppler E/A ratio decreased from 1.04 +/- 0.33 to 0.83 +/- 0.25 (p < 0.02), suggesting that left ventricular diastolic function may have been improved by latissimus dorsi muscle stimulation. Peak oxygen consumption was unaltered (1,633 +/- 530 vs. 1,596 +/- 396 ml/min). CONCLUSIONS: Alterations in left ventricular diastolic rather than systolic function may be responsible for the long-term clinical benefits of cardiomyoplasty.

Regional specificity of peak hyperemic response in patients with congestive heart failure: correlation with peak aerobic capacity.

OBJECTIVES: The aim of this study was to compare peak reactive hyperemic blood flows in the forearm and calf of patients with congestive heart failure and in age- and gender-matched normal subjects. In addition, we attempted to correlate peak oxygen consumption with forearm and calf peak reactive hyperemic flows in the patients with heart failure. BACKGROUND: Disparate results have been reported regarding forearm peak reactive hyperemia in patients with congestive heart failure. Because training significantly increases peak reactive hyperemic flow in normal subjects, we hypothesized that in patients with congestive heart failure who curtail walking because of exertional symptoms, calf peak reactive hyperemic flow would be preferentially attenuated and that impairment of calf vasculature may correlate with peak oxygen consumption. METHODS: Forearm and calf blood flows were measured by venous occlusive plethysmography at rest and after 5 min of arterial occlusion in 46 patients with congestive heart failure and 7 age- and gender-matched normal subjects. Peak oxygen consumption was measured during graded exercise on a bicycle ergometer. RESULTS: Calf peak reactive hyperemic flow was lower in patients with congestive heart failure than in normal subjects (22 +/- 1 vs. 32.5 +/- 3.5 ml/min per 100 ml, p < 0.001), whereas forearm peak reactive hyperemic flows were similar in the two groups. Calf peak reactive hyperemic flow was linearly related to peak oxygen consumption (r = 0.58, p < 0.0001), but forearm peak reactive hyperemic flow was not. Forearm and calf peak reactive hyperemic flows were not related at rest or after 5 min of arterial occlusion in the patients with heart failure. CONCLUSIONS: Calf peak reactive hyperemic flow is reduced in patients with congestive heart failure, whereas forearm peak reactive hyperemic flow is identical to that of age- and gender-matched normal subjects. Calf peak reactive hyperemic flow is linearly related to peak oxygen consumption in patients with congestive heart failure, but forearm peak reactive hyperemic flow is not.

Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure.

Impaired endothelial-dependent vasodilation has been demonstrated in two animal models of congestive heart failure and in the coronary circulation of patients with idiopathic dilated cardiomyopathy. To determine whether this impairment contributes to the abnormal peripheral vasomotor tone in patients with congestive heart failure, the local vascular response to intraarterial infusions of graded concentrations (10(-8) M to 10(-5) M) of acetylcholine (an endothelial-dependent vasodilator) and nitroglycerin (a direct-acting vasodilator) was studied in the superficial femoral artery of 19 patients with congestive heart failure (New York Heart Association classes I to IV) and 6 age-matched normal control subjects. The local vascular response was determined from the arterial blood flow velocity pattern obtained by transcutaneous Doppler ultrasonography. Acetylcholine, 10(-5) M, induced a pattern characteristic of vasodilation in all six normal subjects; mean blood flow velocity for the group significantly increased from 11.9 +/- 2.7 to 44.8 +/- 20.9 cm/s (p less than 0.05). In contrast, the same dose of acetylcholine induced a blood flow velocity pattern characteristic of vasodilation in only 4 of the 19 patients with congestive heart failure. Group mean blood flow velocity did not change significantly. Nitroglycerin, 10(-7) M, induced vasodilation in all 6 normal subjects but in only 1 of 19 patients. Nitroglycerin, 10(-5) M, was administered to 10 patients; all 10 demonstrated a pattern characteristic of vasodilation. Thus, acetylcholine-mediated endothelial-dependent vasodilation appears to be impaired in the peripheral vasculature of patients with congestive heart failure. Both endothelial dysfunction and abnormal vascular smooth muscle responsiveness may contribute to abnormal peripheral vasomotor tone.