Improvement Of Congestive Heart Failure Research Articles

Beta-blockers for congestive heart failure in children.

Beta-blockers are an essential part of standard therapy in adult congestive heart failure and therefore, are expected to be beneficial in children. However, congestive heart failure in children differs from that in adults in terms of characteristics, aetiology, and drug clearance. Therefore, paediatric needs must be specifically investigated. This is an update of a Cochrane review previously published in 2009. To assess the effect of beta-adrenoceptor-blockers (beta-blockers) in children with congestive heart failure. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS up to November 2015. Bibliographies of identified studies were checked. No language restrictions were applied. Randomised, controlled, clinical trials investigating the effect of beta-blocker therapy on paediatric congestive heart failure. Two review authors independently extracted and assessed data from the included trials. We identified four new studies for the review update; the review now includes seven studies with 420 participants. Four small studies with 20 to 30 children each, and two larger studies of 80 children each, showed an improvement of congestive heart failure with beta-blocker therapy. A larger study with 161 participants showed no evidence of benefit over placebo in a composite measure of heart failure outcomes. The included studies showed no significant difference in mortality or heart transplantation rates between the beta-blocker and control groups. No significant adverse events were reported with beta-blockers, apart from one episode of complete heart block. A meta-analysis of left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) data showed a very small improvement with beta-blockers. However, there were vast differences in the age, age range, and health of the participants (aetiology and severity of heart failure; heterogeneity of diagnoses and co-morbidities); there was a range of treatments across studies (choice of beta-blocker, dosing, duration of treatment); and a lack of standardised methods and outcome measures. Therefore, the primary outcomes could not be pooled in meta-analyses. There is not enough evidence to support or discourage the use of beta-blockers in children with congestive heart failure, or to propose a paediatric dosing scheme. However, the sparse data available suggested that children with congestive heart failure might benefit from beta-blocker treatment. Further investigations in clearly defined populations with standardised methodology are required to establish guidelines for therapy. Pharmacokinetic investigations of beta-blockers in children are also required to provide effective dosing in future trials.

Beta-blockers for congestive heart failure in children.

Beta-blockers are an essential part of standard therapy in adult congestive heart failure and therefore, are expected to be beneficial in children. However, congestive heart failure in children differs from that in adults in terms of characteristics, aetiology, and drug clearance. Therefore, paediatric needs must be specifically investigated. This is an update of a Cochrane review previously published in 2009. To assess the effect of beta-adrenoceptor-blockers (beta-blockers) in children with congestive heart failure. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS up to November 2015. Bibliographies of identified studies were checked. No language restrictions were applied. Randomised, controlled, clinical trials investigating the effect of beta-blocker therapy on paediatric congestive heart failure. Two review authors independently extracted and assessed data from the included trials. We identified four new studies for the review update; the review now includes seven studies with 420 participants. Four small studies with 20 to 30 children each, and two larger studies of 80 children each, showed an improvement of congestive heart failure with beta-blocker therapy. A larger study with 161 participants showed no evidence of benefit over placebo in a composite measure of heart failure outcomes. The included studies showed no significant difference in mortality or heart transplantation rates between the beta-blocker and control groups. No significant adverse events were reported with beta-blockers, apart from one episode of complete heart block. A meta-analysis of left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) data showed a very small improvement with beta-blockers.However, there were vast differences in the age, age range, and health of the participants (aetiology and severity of heart failure; heterogeneity of diagnoses and co-morbidities); there was a range of treatments across studies (choice of beta-blocker, dosing, duration of treatment); and a lack of standardised methods and outcome measures. Therefore, the primary outcomes could not be pooled in meta-analyses. There is not enough evidence to support or discourage the use of beta-blockers in children with congestive heart failure, or to propose a paediatric dosing scheme. However, the sparse data available suggested that children with congestive heart failure might benefit from beta-blocker treatment. Further investigations in clearly defined populations with standardised methodology are required to establish guidelines for therapy. Pharmacokinetic investigations of beta-blockers in children are also required to provide effective dosing in future trials.

Tolvaptan Can Improve Clinical Course in Responders

We previously defined "responders" as patients with increases in urine volume (UV) on day 1 after the administration of tolvaptan (TLV), and demonstrated that responders to TLV could be predicted with considerable accuracy by urine osmolality (U-OSM) levels. Responders and non-responders to TLV should be associated with different clinical courses after a certain time following TLV administration. Therefore, the aim of the present study was to validate our definition of responders by clinical parameters 1 week after administration of TLV. Data (n = 85) were obtained from in hospital patients with decompensated heart failure (HF) who had received TLV at 3.75-15 mg daily, and clinical data at 1 week after the administration of TLV were compared with those of baseline. Sixty patients (70.6%) were "responders", in whom UV on day 1 increased after the administration of TLV compared with day 0. "Non-responders" were older, and had higher serum creatinine concentration and lower baseline U-OSM than "responders". Serum creatinine concentration increased significantly in "non-responders", but was unchanged in "responders". Body weight, plasma B-type natriuretic peptide concentration, and HF symptom score decreased significantly in "responders", but remained unchanged in "non-responders". Increases in UV after the first administration of TLV were closely correlated with improvement of congestive HF after 1 week of TLV treatment, which verified our definition of "responders" to TLV.

Respiratory sound energy and its distribution patterns following clinical improvement of congestive heart failure: a pilot study.

BackgroundAlthough congestive heart failure (CHF) patients typically present with abnormal auscultatory findings on lung examination, respiratory sounds are not normally subjected to additional analysis. The aim of this pilot study was to examine respiratory sound patterns of CHF patients using acoustic-based imaging technology. Lung vibration energy was examined during acute exacerbation and after clinical improvement.MethodsRespiratory sounds throughout the respiratory cycle were captured using an acoustic-based imaging technique. Twenty-three consecutive CHF patients were imaged at the time of presentation to the emergency department and after clinical improvement. Digital images were created (a larger image represents more homogeneously distributed vibration energy of respiratory sound). Geographical area of the images and respiratory sound patterns were quantitatively analyzed. Data from the CHF patients were also compared to healthy volunteers.ResultsThe median (interquartile range) geographical areas of the vibration energy image of acute CHF patients without and with radiographically evident pulmonary edema were 66.9 (9.0) and 64.1(9.0) kilo-pixels, respectively (p < 0.05). After clinical improvement, the geographical area of the vibration energy image of CHF patients without and with radiographically evident pulmonary edema were increased by 18 ± 15% (p < 0.05) and 25 ± 16% (p < 0.05), respectively.ConclusionsWith clinical improvement of acute CHF exacerbations, there was more homogenous distribution of lung vibration energy, as demonstrated by the increased geographical area of the vibration energy image.

Improvement of Congestive Heart Failure after Octreotide and Transsphenoidal Surgery in a Patient with Acromegaly

A 59-year-old man was admitted because of congestive heart failure. He was suspected to have acromegaly, and magnetic resonance imaging revealed a pituitary macroadenoma. Endocrine examination revealed elevated plasma levels of growth hormone (GH) and insulin-like growth factor (IGF)-1, and an oral glucose tolerance test failed to suppress plasma GH levels, consistent with the diagnosis of GH-producing pituitary tumor. Treatment with octreotide, followed by transsphenoidal surgery resulted in normalization of plasma GH/IGF-1 levels, accompanied by the improvement of cardiac function. Thus, it is suggested that excess GH/IGF-1 axis is involved in the development of acromegaly-related cardiomyopathy in the present case.

Decitabine Improves Clinical Outcomes in Severely Ill Sickle Cell Disease Patients Who Have Exhausted Standard of Care Options.

Interventions such as immunization, penicillin prophylaxis, hydroxyurea and transfusion have extended life in patients with sickle cell disease (SCD). Nonetheless, these interventions are limited by toxicity or effectiveness; continued substantial morbidity and mortality in SCD indicates the need for better disease modification. In previous phase I/II clinical trials, 13 of 13 patients treated with the DNA hypomethylating agent decitabine responded with clinically significant fetal hemoglobin and total hemoglobin elevation and improvement in surrogate clinical end-points. However, in these early studies, no clinical end-points were measured and further studies have been delayed by funding issues. We describe an off-label experience in four patients with severe SCD that suggestsi.remarkable clinical effectiveness in patients who have exhausted standard of care and are severely ill;ii.tolerability even in the severely ill;iii.a mechanism of action based on increased reticulocytosis in addition to increased fetal hemoglobin.All four patients had multiple alloantibodies and red-cell auto-antibodies that limited availability and increased risks of transfusion, and had previously been treated with hydroxyurea with continued clinical deterioration. Three of the four patients had relative reticulocytopenia (absolute reticulocyte count <250x109/L and hemoglobin <9g/dl) and were receiving erythropoietin or darbopoietin for more than 8 weeks with continued progressive anemia and progressive congestive heart failure. All four patients were ECOG performance status 3 and ineligible for available clinical trials. Based on the clinical trial experience conducted at our institution, decitabine therapy at 0.1–0.2 mg/kg 1–2X/week was initiated in these patients not for research purposes but with the intent to produce direct clinical benefit. The limited clinical data and potential for unanticipated toxicity was discussed in full with each patient and family members. IRB approval was obtained for a retrospective chart review. No decitabine related adverse events occurred. All patients demonstrated >2g/dl increases in hemoglobin levels with an associated improvement in clinical status - decrease in pain, improvement in performance status, improvement in congestive heart failure symptoms/signs. Upward trends in the platelet and reticulocyte counts concurrent with downward trends in the neutrophil counts were consistent with previously observed effects of low dose decitabine or the related compound 5-azacytidine. Clinically significant neutropenia was avoided by dose reductions that did not reverse the improved hemoglobin levels. The differentiation altering effects of low dose decitabine relieve SCD anemia by decreasing hemolysis (through elevated HbF) and increasing reticulocytosis. Previous clinical trials, and this off-label experience, suggest that decitabine holds remarkable promise as a disease modifying agent for SCD and β-thalassemia. Further clinical trials to confirm this impression should be supported.

PPARδ Activation Normalizes Cardiac Substrate Metabolism and Reduces Right Ventricular Hypertrophy in Congestive Heart Failure

Previously, it was shown that selective deletion of peroxisome proliferator activated receptor delta (PPARdelta) in the heart resulted in a cardiac lipotoxicity, hypertrophy, and heart failure. The aim of the present study was to determine the effects of chronic and selective pharmacological activation of PPARdelta in a model of congestive heart failure. PPARdelta-specific agonist treatment (GW610742X at 30 and 100 mg/kg/day for 6-9 weeks) was initiated immediately postmyocardial infarction (MI) in Sprague-Dawley rats. Magnetic resonance imaging/spectroscopy was used to assess cardiac function and energetics. A 1-(13)C glucose clamp was performed to assess relative cardiac carbohydrate versus fat oxidation. Additionally, cardiac hemodynamics and reverse-transcription polymerase chain reaction gene expression analysis was performed. MI rats had significantly reduced left ventricle (LV) ejection fractions and whole heart phosphocreatine/adenosine triphosphate ratio compared with Sham animals (reduction of 43% and 14%, respectively). However, GW610742X treatment had no effect on either parameter. In contrast, the decrease in relative fat oxidation rate observed in both LV and right ventricle (RV) following MI (decrease of 58% and 54%, respectively) was normalized in a dose-dependent manner following treatment with GW610742X. These metabolic changes were associated with an increase in lipid transport/metabolism target gene expression (eg, CD36, CPT1, UCP3). Although there was no difference between groups in LV weight or infarct size measured upon necropsy, there was a dramatic reduction in RV hypertrophy and lung congestion (decrease of 22-48%, P<0.01) with treatment which was associated with a >7-fold decrease (P<0.05) in aterial natriuretic peptide gene expression in RV. Diuretic effects were not observed with GW610742X. In conclusion, chronic treatment with a selective PPARdelta agonist normalizes cardiac substrate metabolism and reduces RV hypertrophy and pulmonary congestion consistent with improvement in congestive heart failure.

Improvement of Congestive Heart Failure by Upgrading of Conventional to Resynchronization Pacemakers

To compare the clinical response of patients with right ventricular apical pacing (RVAP) upgraded to cardiac resynchronization therapy (CRT) to that of previously nonpaced heart failure (HF) patients who had de novo CRT implantation. The role of CRT in patients with wide QRS and HF due to RVAP is less well established than in other CRT candidates. Ninety-eight consecutive patients with CRT were studied (mean age 70, mean ejection fraction 0.23). Group A: patients having RVAP prior to CRT implantation (n = 25), group B: patients without prior RVAP (n = 73). Clinical and echocardiographic parameters were recorded prior to, and 3 months after, CRT implantation. Group A patients had a wider QRS at baseline compared to group B (203 +/- 32 ms vs 163 +/- 30 ms respectively, P < 0.001), and a shorter 6-minute walking distance (222 +/- 118 m vs 362 +/- 119 m, respectively, P < 0.005). Otherwise, clinical and echocardiographic parameters were not different. At follow up, group A patients had an average 0.7 +/- 0.5 decrease in their NYHA functional class, compared to 0.3 +/- 0.7 in group B patients (P < 0.05). Six-minute walking distance increased by 93 +/- 113 m in group A, versus 36 +/- 120 m in group B (P = 0.22). There was no difference in echocardiographic response to CRT between the groups. HF patients with prior RVAP demonstrate clinical improvement after upgrading to CRT that is comparable, and in some aspects, even better than that observed in HF patients with native conduction delay who undergo de novo CRT implantation.

Persistent pulmonary hypertension in a neonate with vein of Galen arteriovenous malformation.

Vein of Galen aneurysmal malformation (VGAM) often leads to death in the neonatal period, mainly due to congestive heart failure. Chronic and excessive pulmonary flow in utero and postnatally is attributed to large VGAM and right ventricular overload. We report a male neonate with VGAM complicated by severe heart failure and persistent pulmonary hypertension. Endovascular coil embolization of VGAM was performed, resulting in improvement of congestive heart failure; however, severe persistent pulmonary hypertension led to death 2 days after the embolization. Postmortem examination showed marked right and left ventricular hypertrophy and impressive muscular thickening of intra-alveolar arterioles. Neonatal embolization seems to be beneficial only in babies without suprasystemic pulmonary hypertension. Therefore, early delivery and repair of VGAM should be considered before the onset of persistent pulmonary hypertension.

The Association Between Cholesterol and Mortality in Heart Failure Comparison Between Patients With and Without Coronary Artery Disease

Hypercholesterolemia is a risk factor for development of coronary artery disease (CAD), however, several reports have suggested that low serum cholesterol is associated with a worse prognosis in patients with congestive heart failure (CHF). The objective of this study was to determine the prognostic value of cholesterol for CHF. The study subjects consisted of 133 consecutive patients hospitalized in our institution for progressive heart failure from April 2000 to March 2003. Thirty-two percent of the patients had CAD. After improvement of congestive heart failure and discharge from the hospital, lipid profiles, including serum total cholesterol (TC), triglycerides, and high and low density lipoprotein cholesterol (HDL, LDL, respectively), were obtained. During the follow-up period (2.3 +/- 0.9 years), 21 patients died. There was a significant difference between survivors and nonsurvivors in HDL (53 +/- 15, 43 +/- 15 mg/dL, P = 0.01), but no differences were observed in other variables. In patients with CAD, survivors had significantly lower TC concentrations (179 +/- 30 versus 246 +/- 55 mg/dL, P = 0.004), although in patients without CAD, survivors had significantly higher TC concentrations (203 +/- 37 versus 170 +/- 40 mg/dL, P = 0.02). Multivariate analysis showed high TC predicted a worse outcome in patients with CAD (odds ratio (OR) = 1.052, 95% confidence interval (CI) 1.002-1.104, P = 0.04), but a better outcome in patients without CAD (OR = 0.972, 95% CI 0.948-0.997, P = 0.03), independent of age, gender, medication, and complications. Thus, low serum cholesterol is associated with an improved outcome in patients with CAD, while it predicts a worse outcome in patients without CAD.

Peroxisome proliferator-activated receptor activators inhibit lipopolysaccharide-induced tumor necrosis factor-alpha expression in neonatal rat cardiac myocytes.

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. Recently, PPAR activators have been shown to inhibit the production of proinflammatory cytokines in macrophages or vascular smooth muscle cells. It has been reported that tumor necrosis factor-alpha (TNF-alpha) expression is elevated in the failing heart and that TNF-alpha has a negative inotropic effect on cardiac myocytes. Therefore, we examined the effects of PPARalpha and PPARgamma activators on expression of TNF-alpha in neonatal rat cardiac myocytes. Northern blot analysis revealed expression of PPARalpha and PPARgamma mRNA in cardiac myocytes. Immunofluorescent staining demonstrated that both PPARalpha and PPARgamma were expressed in the nuclei of cells. When cardiac myocytes were transfected with PPAR responsive element (PPRE)-luciferase reporter plasmid, both PPARalpha and PPARgamma activators increased the promoter activity. Cardiomyocytes were stimulated with lipopolysaccharide (LPS), and the levels of TNF-alpha in the medium were measured by ELISA. After exposure to LPS, the levels of TNF-alpha significantly increased. However, pretreatment of myocytes with PPARalpha or PPARgamma activators decreased LPS-induced expression of TNF-alpha in the medium. Both PPARalpha and PPARgamma activators also inhibited LPS-induced increase in TNF-alpha mRNA in myocytes. In addition, electrophoretic mobility shift assays demonstrated that PPAR activators reduced LPS-induced nuclear factor-kappaB activation. These results suggest that both PPARalpha and PPARgamma activators inhibit cardiac expression of TNF-alpha in part by antagonizing nuclear factor-kappaB activity and that treatment with PPAR activators may lead to improvement in congestive heart failure.

Effects of imidapril on NOS expression and myocardial remodelling in failing heart of Dahl salt-sensitive hypertensive rats

To elucidate the relationship between renin-angiotensin system and nitric oxide in hypertensive heart failure, we evaluated the effects of long-term treatment with imidapril, angiotensin-converting enzyme inhibitor, on endothelial-cell nitric oxide synthase (eNOS) and inducible NOS (iNOS) expression in the left ventricle (LV) and its relation to myocardial remodelling in failing heart of Dahl salt-sensitive hypertensive rats (DS) fed a high-salt diet. In DS rats fed an 8% NaCl diet after the age of 6 weeks, a stage of concentric left ventricular hypertrophy at 11 weeks (DSLVH) was followed by a distinct stage of fatal left ventricular failure with chamber dilatation at 18 weeks (DSCHF). Imidapril (DSCHF-I, n = 7, 1 mg/kg/day, subdepressor dose) or vehicle (DSCHF-V, n = 7) were given from DSLVH to DSCHF stage for 7 weeks, and age-matched (18 weeks) Dahl salt-resistant rats fed the same diet were served as control group (DR-C, n = 7). Markedly increased left ventricular end-diastolic diameter and reduced fractional shortening in DSCHF-V was significantly ameliorated in DSCHF-I using transthoracic echocardiography. The level of eNOS mRNA and protein in the LV was significantly suppressed in DSCHF-V compared with DR-C, and significantly increased in DSCHF-I compared with DR-C and DSCHF-V. The iNOS mRNA and protein and the fibrosis factor expression of type I collagen mRNA were significantly increased in DSCHF-V compared with DR-C, and significantly decreased in DSCHF-I compared with DSCHF-V. DSCHF-V demonstrated a significant increase in wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis. These changes in the microvasculature were improved significantly by imidapril. Subdepressor dose of imidapril may ameliorate the endothelial damage not only by inhibiting production of angiotensin II but also by promoting eNOS and inhibiting iNOS mRNA and protein expression in the LV, and this increased eNOS mRNA and protein level may have a role in the improvement of congestive heart failure and myocardial remodelling.

Renal Effects of L-DOPA in Heart Failure

We examined whether low-dose L-DOPA treatment induces natriuresis and diuresis in patients with congestive heart failure who have cardiac decompensation despite treatment with digoxin, a diuretic, and an angiotensin-converting enzyme inhibitor and who respond acutely to intravenously infused dopamine. In a randomized, double-blind, placebo-controlled crossover study, 11 patients with severe congestive heart failure received L-DOPA (0.10 g, p.o., t.i.d., for 1 day and then 0.25 g, p.o., t.i.d., for 2 days after a washout period of > or = 1 day), with assessments of plasma and urinary levels of catechols, urinary volume, and sodium content, and clinical and laboratory measures of improvement of congestive heart failure. L-DOPA elicited short-term, dose-related increases in urinary volume and sodium excretion. At the 0.10-g dose, L-DOPA increased plasma L-DOPA levels and urinary L-DOPA excretion by about fivefold, whereas at the 0.25-g dose, L-DOPA increased plasma and urinary L-DOPA by >50-fold. Twenty-four-hour urinary dopamine excretion increased by about fivefold after the low dose of L-DOPA and approximately 50-fold after the high dose. The results demonstrate that oral L-DOPA treatment can produce beneficial natriuretic and diuretic effects in selected patients with congestive heart failure. The bioavailability of oral L-DOPA appears to vary with the dose. These results support findings from previous studies about beneficial cardiac functional effects of L-DOPA in patients with refractory heart failure.

Relation of functional improvement in congestive heart failure after quinapril therapy to peripheral limitation

Angiotensin-converting enzyme inhibitors have been shown to increase maximal muscle blood flow in parallel to peakV̇O2 in patients with congestive heart failure (CHF). Whether this increase shifts factors limiting peak aerobic capacity from periphery (skeletal muscle or vessels) to central factors (cardiac or respiratory) is unknown. Comparison of peak oxygen consumption (V̇O2) obtained during leg cycling (V̇O2 leg) with peakV̇O2 obtained during combined leg cycling and arm cranking (V̇O2 arm + leg) allows determination of the relative role of central or peripheral factors. We comparedV̇O2 leg withV̇O2 arm + leg before and after 3 months of therapy with quinapril 40 mg in 16 patients with CHF (age 53 ± 13 years) due to left ventricular systolic dysfunction (ejection fraction 0.25 ± 0.07). Before quinapril,V̇O2 arm + leg was significantly higher thanV̇O2 leg (19.0 ± 3.3 vs 16.9 ± 3.8 ml/kg/min, p < 0.001), whereas after therapy these 2 values were similar (20.3 ± 4.3 vs 21.0 ± 4.3 ml/kg/min; p = NS), indicating that patients were no longer limited by peripheral factors. Besides,V̇O2 leg increase after therapy was higher in patients in whom difference betweenV̇O2arm + leg andV̇O2 leg was the greatest (i.e., in patients who were initially more limited by peripheral factors). Simultaneously, calf peak reactive hyperemia and circumference significantly increased, indicating an improvement in vascular dilating capacity and an increase in skeletal muscle mass. No significant modification occurred in the forearm. Thus, patients who improved the most after 3 months of quinapril therapy were those who were initially limited by peripheral factors. The restricting role of these factors was reduced after quinapril therapy.

うっ血性心不全の改善に伴いテオフィリントラフ濃度の上昇を認めた症例

うっ血性心不全の改善に伴いテオフィリントラフ濃度の上昇を認めた症例

Early improvement in congestive heart failure after correction of secondary mitral regurgitation in end-stage cardiomyopathy

Mitral regurgitation frequently complicates dilated cardiomyopathy, aggravates volume overload of the left ventricle, and contributes to symptoms of congestive heart failure. This study was performed to assess the impact of mitral valve reconstruction in nine consecutive patients with severe mitral regurgitation resulting from end-stage dilated cardiomyopathy. Clinical and echocardiographic follow-up were obtained 17 ± 5 and 16 ± 6 weeks after surgery, respectively. There were no operative or early deaths. All patients noted symptomatic improvement postoperatively, and there was a decrease of at least one New York Heart Association functional class (3.9 ± 0.3 to 1.7 ± 0.5, p < 0.001). Quantitative echocardiography/Doppler demonstrated a small but significant decrease in left ventricular end-diastolic volume (317 ± 111 ml to 291 ± 105 ml, p = 0.04) and increases in ejection fraction (18 ± 5% to 24 ± 9%, p = 0.02) and forward cardiac output (3.1 ± 1.0 to 4.6 ± 0.8 Umin, p < 0.01) on follow-up. Mitral valve reconstruction for the correction of mitral regurgitation in patients with end-stage dilated cardiomyopathy results in improved symptomatic status on early follow-up accompanied by evidence of improvement in left ventricular performance. (Ann HEART J 1995;129:1165-70.)

901-75 Early Improvement in Congestive Heart Failure Following Correction of Secondary Mitral Regurgitation in End-Stage Cardiomyopathy

Mitral regurgitation (MR) frequently complicates cardiomyopathy (CM) and contributes to symptoms of congestive heart failure (CHF). This study was undertaken to assess the changes in CHF and left ventricular (LV) systolic performance following mitral valve reconstruction (MVR) in patients with severe MR secondary to end-stage dilated CM. Nine consecutive patients (age 64 ± 10 yrs) with severe LV dysfunction (ejection fraction [EF] 18 ± 5% [10–25%]). severe MR and NYHA Class III (n = 1) or IV (n = 8) CHF despite aggressive medical therapy underwent MVR. All patients were receiving therapy including digoxin, diuretics and afterload reducers. Two patients were awaiting heart transplantation. There were no operative deaths or deaths on 17 ± 5 (8-24) week follow-up (PostOp). All patients noted symptomatic improvement NYHA Class improved from 3.9 ± 0.3 pre-operatively (PreOp) to 1.7 ± 0.5 (p &lt; 0.001) Diuretic requirements were markedly lower for 5 of 9 patients and stable for the remaining 4. Ouantitative 2D echo/Doppler was performed on all patients PreOp and on 8 of 9 patients PostOp. MR was absent or mild on follow-up in all. Matched PreOp and PostOp LV end-diastolic volume (EDV), EF, forward cardiac output (CO) and regurgitant fraction (RF) were compared for change (Δ): EDV(cc) EF(%) CO(L/min) RF(%) PreOp 317 ± 111 18 ± 5 3.1 ± 1.0 70 ± 12 PestOp 291 ± 106 24 ± 9 4.6 ± 0.8 13 ± 10 Δ -26 ± 31 +6 ± 5 +15 ± 0.9 -57 ± 15 P 0.04 0.02 0004 &lt;0.001 Improvement in CHF occurred after MVR in all patients on short-term follow-up, accompanied by lower LV end-diastolic volume and increased EF and forward cardiac output Mitral reconstruction may be a new strategy for the treatment of patients with severe MR complicating end-stage cardiomyopathy.

Clinical and left ventricular function outcomes up to five years after dynamic cardiomyoplasty

Improvement in congestive heart failure and left ventricular function after dynamic cardiomyoplasty has been reported in patients with severe cardiomyopathies, but the long-term effects of this procedure remain unclear. In this investigation 31 patients undergoing cardiomyoplasty for treatment of idiopathic dilated cardiomyopathy were annually investigated with radionuclide scintigraphy, Doppler echocardiography, and right-sided heart catheterization. They were in New York Heart Association functional class III or IV before the operation. No hospital deaths occurred, but one patient with progressive heart failure required urgent heart transplantation 42 days after cardiomyoplasty. The other patients were followed up from 6 to 70 months (mean 25.6 months) and 12 patients died at late follow-up. Actuarial survivals were 86% at 1 year, 61.4% at 2 years, and 42.5% at 3 to 5 years of follow-up. Multivariate analysis of factors influencing outcome showed that long-term survival was significantly affected by preoperative functional class and pulmonary vascular resistance. Functional class improved from 3.2 ± 0.4 to 1.7 ± 0.7 in the surviving patients ( p < 0.01). Furthermore, left ventricular ejection fraction improved from 19.8% ± 3% to 23.9% ± 7.2% ( p < 0.01), and significant changes in stroke index, arterial pressure, pulmonary wedge pressure, and left ventricular stroke work index were also found at 6 months of follow-up. In the late postoperative period, the left ventricular ejection fraction tended to decrease and returned to preoperative levels at 5 years, whereas hemodynamic variables did not change significantly. Thus, despite the tendency of the left ventricular ejection fraction to decrease at late follow-up, the long-term course of these patients seems to be characterized by the maintenance of hemodynamic improvement. However, long-term survival after cardiomyoplasty is limited by the severity of the patient's condition before the operation. (J T HORAC C ARDIOVASC S URG 1995;109:353-63)

Clinical studies of enalapril treatment for patients with severe congestive heart failure.

The clinical efficacy of enalapril was investigated in 21 patients with severe heart failure. For each subject, the following parameters were compared before and one month after enalapril maintenance treatment. NYHA functional class, Killip's class, cardiothoracic ratio (CTR), left ventricular (LV) function estimated by echocardiography and gated equilibrium radionuclide angiography, Holter ECG recordings, serum digoxin concentration (SDC), plasma remin activity, plasma aldosterone concentration, plasma norepinephrine concentration (PNE), etc. Short- and long-term hemodynamic responses to enalapril were also studied, with simultaneous measurement of enalapril concentration by radioimmunoassay. After maintenance therapy, patients showed a significant improvement as judged by NYHA functional class, Killip's class, and CTR. The LV fractional shortening and the ejection fraction significantly increased. The frequency of ventricular tachycardia showed a significant tendency to decrease after the therapy. The SDCs were unchanged, which indicates no pharmacokinetic drug interaction between digoxin and enalapril. Hemodynamic assessment showed a reduction in systemic vascular resistance, a reduction in mean blood pressure, and an increase in the cardiac index. No major side effects were observed during the study period. According to a multivariate analysis, the coefficient of determination of PNE was the highest for the final global improvement rating. This may reflect the neurohormonal improvement of congestive heart failure by enalapril therapy. In conclusion, enalapril is recommended for treating patients with severe CHF.

Thirty-year follow-up of superior vena cava-pulmonary artery (Glenn) shunts

The first superior vena cava-pulmonary artery shunt (Glenn shunt) in our series was performed in February 1958. From then through September 1988, 91 patients have undergone this procedure for a wide variety of congenital defects. We here report follow-up data available on all patients. Ages ranged from 2 days to 46 years (mean 6.8). Diagnoses were as follows: tricuspid atresia, 27; single ventricle, 22; tetralogy of Fallot, 14; D-transposition of the great arteries, ventricular septal defect, and pulmonary stenosis, 9; D-transposition, 5; Ebstein's anomaly, 4; pulmonary atresia + intact septum, 4; and others, 6. The hospital mortality rate was 7.7% (one death in the last 53 patients, 1.9%). Five deaths occurred in patients less than 6 months old. There were 20 late deaths (22%) with actuarial survival rates of 84% and 66% at 10 and 20 years, respectively. Pulmonary arteriovenous fistula formation was seen in 18 patients (19.7%), six of whom have undergone therapeutic embolization with improvement in saturation. The prevalence of pulmonary arteriovenous fistula increases with time after shunt. No long-term shunt thrombosis or stricture formation was seen. Fifty percent of shunts were still functioning at 20 years. Palliation was limited because of decrease in blood flow to the contralateral pulmonary artery, collaterals between the inferior and superior venae cavae, and pulmonary arteriovenous fistula formation. Improvement in saturation was obtained in eight otherwise inoperable patients by creation of a right axillary arteriovenous fistula up to 19 years after the Glenn shunt. Three patients had conversion of a Blalock-Taussig shunt to a Glenn shunt with improvement in congestive heart failure. Twenty-six patients have undergone a Fontan procedure with two deaths. Compared with the group having a Fontan procedure without a prior Glenn operation, there was no difference in early or late mortality. Thirty years after a Glenn shunt, the first patient in this series is working full time after having undergone a modified Fontan procedure in 1981. We conclude that the Glenn connection, usually with supplemental procedures to enhance oxygenation, has provided excellent physiologic palliation with low mortality up to 30 years with no late thrombosis or stricture formation. The incidence of pulmonary arteriovenous fistula increases with time and can be effectively treated with embolization. Physiologic repair after the Glenn shunt carries a low mortality. Although currently used infrequently, superior vena cava-pulmonary artery shunting remains a useful method of palliation in selected patients.(ABSTRACT TRUNCATED AT 400 WORDS)