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: ObjectivesThis study evaluated the role of clinical rescreening of family members at risk for familial dilated cardiomyopathy (FDC).: BackgroundFamilial dilated cardiomyopathy is a genetic cardiomyopathy that usually is transmitted in an autosomal dominant pattern and may underlie from one-quarter to one-half of idiopathic dilated cardiomyopathy (IDC) diagnoses. Thus, FDC may present with advanced heart failure (HF) or sudden cardiac death (SCD). Because FDC may respond to medical intervention, we have previously recommended that screening of first-degree relatives (parents, siblings, children) of patients diagnosed with IDC be undertaken to rule out FDC, and that with a diagnosis of FDC in the kindred, unaffected but at-risk family members be rescreened every three to five years.: MethodsFollow-up screening (history, examination, electrocardiogram, echocardiography) of a large family with FDC was performed six years after initial screening.: ResultsOf 68 family members who underwent rescreening, two (one with left ventricular enlargement only, one with a left bundle branch block) presented with advanced HF and SCD, respectively. Two additional subjects, asymptomatic at initial screening, were also affected with FDC at follow-up.: ConclusionsConsiderable vigilance for disease presentation and progression is indicated in at-risk members of a kindred with FDC, especially those with incipient FDC. [Copyright &y& Elsevier]

Because of the increasing number of pharmacologic strategies available for treatment of heart failure (HF), the time has come to reassess the adequacy of end points used to evaluate therapeutic efficacy. Interest in the use of surrogate end points in clinical studies is increasing. A surrogate end point is defined as a measurement that can substitute for a true end point for the purpose of comparing specific interventions or treatments in a clinical trial. A true end point is one that is of clinical importance to the patient (e.g., mortality or quality of life), whereas a surrogate end point is one biologically closer to the disease process (e.g., ejection fraction or left ventricular volume in HF). The prime motivation for the use of a surrogate end point concerns the possible reduction in sample size or trial duration. Such reductions have important cost implications and in some cases may influence trial feasibility. Another, perhaps more important, aspect of measuring surrogate end points is that they increase our understanding of the mechanism of action of drugs and thus may help physicians to take a more enlightened approach in managing their patients. In this article we have analyzed the possible potentials of the surrogate end points in clinical studies of patients with chronic HF. Other uses of possible surrogates are discussed, and the limitations in finding true surrogates are mentioned. At this time we conclude there is no well established surrogate in HF. [Copyright &y& Elsevier]

: ObjectivesWe sought to assess whether aortic valve replacement (AVR) among patients with severe aortic stenosis (AS), severe left ventricular (LV) dysfunction and a low transvalvular gradient (TVG) is associated with improved survival.: BackgroundThe optimal management of patients with severe AS with severe LV dysfunction and a low TVG remains controversial.: MethodsBetween 1990 and 1998, we evaluated 68 patients who underwent AVR at our institution (AVR group) and 89 patients who did not undergo AVR (control group), with an aortic valve area ≤0.75 cm2, LV ejection fraction ≤35% and mean gradient ≤30 mm Hg. Using propensity analysis, survival was compared between a cohort of 39 patients in the AVR group and 56 patients in the control group.: ResultsDespite well-matched baseline characteristics among propensity-matched patients, the one- and four-year survival rates were markedly improved in patients in the AVR group (82% and 78%), as compared with patients in the control group (41% and 15%; p < 0.0001). By multivariable analysis, the main predictor of improved survival was AVR (adjusted risk ratio 0.19, 95% confidence interval 0.09 to 0.39; p < 0.0001). The only other predictors of mortality were age and the serum creatinine level.: ConclusionsAmong select patients with severe AS, severe LV dysfunction and a low TVG, AVR was associated with significantly improved survival. [Copyright &y& Elsevier]

: ObjectivesThe purpose of this study was to determine the mechanisms of sudden death (SD) in patients with ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) treated with an implantable cardioverter defibrillator (ICD).: BackgroundDespite ICD therapy, some patients with VT/VF still die suddenly. Optimal ICD use requires determination of the mechanisms of these residual SDs.: MethodsWe reviewed 320 patient deaths during trials of Medtronic transvenous ICD systems (Medtronic Inc., Minneapolis, Minnesota). Sudden deaths were further categorized according to mechanism. Post-shock electromechanical dissociation (EMD) describes a scenario where VT/VF was appropriately detected and treated by an ICD shock that restored a physiologic rhythm, but death still occurred immediately by EMD.: ResultsA mode of death could be ascribed for 317 patients—90 (28%) were sudden, 156 (49%) were nonsudden cardiac, and 71 (22%) were noncardiac. A mechanism of SD was proposed for 68 patients—20 (29%) had post-shock EMD, 17 (25%) had VT/VF uncorrected by shocks, 11 (16%) had primary electromechanical dissociation, 9 (13%) had incessant VT/VF, 5 (7%) had VT/VF after their ICD was deactivated or removed, and 6 (9%) had single instances of various other terminal events. Only New York Heart Association functional class independently predicted SD by post-shock EMD.: ConclusionsThe most common mechanism of SD in patients with an ICD is VT/VF treated with an appropriate shock followed by EMD. As this mechanism accounted for 29% of the SDs to which a cause could be ascribed, this mechanism of SD warrants further investigation. [Copyright &y& Elsevier]

: ObjectivesThe aim of this study was to evaluate the relationships between echocardiographic findings and clinical outcomes in patients with severe primary pulmonary hypertension (PPH).: BackgroundPrimary pulmonary hypertension is associated with abnormalities of right heart structure and function that contribute to the poor prognosis of the disease. Echocardiographic abnormalities associated with PPH have been described, but the prognostic significance of these findings remains poorly characterized.: MethodsEchocardiographic studies, invasive hemodynamic measurements and 6-min walk tests were performed and outcomes prospectively followed in 81 patients with severe PPH. Subjects were participants in a 12-week randomized trial examining the effects of prostacyclin plus conventional therapy compared with conventional therapy alone.: ResultsDuring the mean follow-up period of 36.9 ± 15.4 months, 20 patients died and 21 patients underwent transplantation. Pericardial effusion (p = 0.003) and indexed right atrial area (p = 0.005) were predictors of mortality. Pericardial effusion (p = 0.017), indexed right atrial area (p = 0.012) and the degree of septal shift in diastole (p = 0.004) were predictors of a composite end point of death or transplantation. In multivariable analyses incorporating clinical, hemodynamic and echocardiographic variables, pericardial effusion and an enlarged right atrium remained predictors of adverse outcomes. Six-minute walk results, mixed venous oxygen saturation and initial treatment randomization were also independently associated with a poor prognosis.: ConclusionsPericardial effusion, right atrial enlargement and septal displacement are echocardiographic abnormalities that reflect the severity of right heart failure and predict adverse outcomes in patients with severe PPH. These characteristics may help identify patients appropriate for more intensive medical therapy or earlier transplantation. [Copyright &y& Elsevier]

: ObjectivesThis study pools data from published series examining late survival with revascularization versus medical therapy after myocardial viability testing in patients with severe coronary artery disease (CAD) and left ventricular (LV) dysfunction.: BackgroundPrevious observational studies have suggested survival benefit in such patients if they are revascularized when myocardial viability is detected on imaging tests.: MethodsA MEDLINE database search returned 24 viability studies reporting patient survival using thallium perfusion imaging, F-18 fluorodeoxyglucose metabolic imaging or dobutamine echocardiography. Annual death rates were extracted, pooled and analyzed with a random effects model. The risk-adjusted relationship between severity of LV dysfunction, presence of viability and survival benefit associated with revascularization was assessed by meta-regression.: ResultsThere were 3,088 patients (2,228 men), ejection fraction 32 ± 8%, followed for 25 ± 10 months. In patients with viability, revascularization was associated with 79.6% reduction in annual mortality (16% vs. 3.2%, chi-square = 147, p < 0.0001) compared with medical treatment. Patients without viability had intermediate mortality, trending to higher rates with revascularization versus medical therapy (7.7% vs. 6.2%, p = NS). Patients with viability showed a direct relationship between severity of LV dysfunction and magnitude of benefit with revascularization (p < 0.001). There was no measurable performance difference for predicting revascularization benefit between the three testing techniques.: ConclusionsThis meta-analysis demonstrates a strong association between myocardial viability on noninvasive testing and improved survival after revascularization in patients with chronic CAD and LV dysfunction. Absence of viability was associated with no significant difference in outcomes, irrespective of treatment strategy. [Copyright &y& Elsevier]

Because the use of herbal therapies in the U.S. is escalating, it is essential to be aware of clinical and adverse effects, doses and potential drug-herb interactions. A consumer poll in 1998 indicated that one-third of respondents use botanical remedies, and nearly one in five taking prescription medications also used herbs, high-dose dietary supplements or both. An estimated 15 million adults are at risk for potential adverse interactions involving prescription medications and herbs or vitamin supplements, yet most practicing physicians have little knowledge of herbal remedies or their effects. Herbal products are marketed without the proof of efficacy and safety that the Food and Drug Administration (FDA) requires of drugs. The Dietary Supplement and Health Education Act of 1994 allocates responsibility to manufacturers for ensuring safety and efficacy with no specific requirements to submit documentation. Manufacturers may state a product’s physiologic effects but may not make claims for the treatment or cure of specific diseases. Consumers and practitioners have little information about product safety, contraindications, interactions or effectiveness and are reliant on manufacturers to provide accurate labeling. Recently, the growing number of foods with herbs has raised concerns at the FDA, which requires evidence that food additives are safe. Considering that the growing appeal of herbal remedies is likely to continue, physicians, particularly cardiologists, must become familiar with the available cardiovascular information on herbs. This review highlights the existing data on the efficacy, adverse effects and interactions for herbal therapies that impact on the cardiovascular system. [Copyright &y& Elsevier]

: ObjectivesWe investigated the prevalence of lamin A/C (LMNA) gene defects in familial and sporadic dilated cardiomyopathies (DCM) associated with atrioventricular block (AVB) or increased serum creatine-phosphokinase (sCPK), and the corresponding changes in myocardial and protein expression.: BackgroundIt has been reported that familial DCM, associated with conduction disturbances or variable myopathies, is causally linked to LMNA gene defects.: MethodsThe LMNA gene and myocardial ultrastructural and immunochemical changes were analyzed in 73 cases of DCM (49 pure, 15 with AVB [seven familial, eight sporadic], 9 with increased sCPK), four cases of familial AVB and 19 non-DCM heart diseases. The normal controls included eight heart donor biopsies for tissue studies and 107 subjects for LMNA gene studies.: ResultsFive novel LMNA mutations (K97E, E111X, R190W, E317K, four base pair insertion at 1,713 cDNA) were identified in five cases of familial autosomal dominant DCM with AVB (5/15: 33%). The LMNA expression of the myocyte nuclei was reduced or absent. Western blot protein analyses of three hearts with different mutations showed an additional 30-kDa band, suggesting a degrading effect of mutated on wild-type protein. Focal disruptions, bleb formation and nuclear pore clustering were documented by electron microscopy of the myocyte nuclear membranes. None of these changes and no mutations were found in the nine patients with DCM and increased sCPK or in the disease and normal controls.: ConclusionsThe LMNA gene mutations account for 33% of the DCMs with AVB, all familial autosomal dominant. Increased sCPK in patients with DCM without AVB is not a useful predictor of LMNA mutation. [Copyright &y& Elsevier]

: ObjectivesThe aim of this study was to evaluate the relationship between plasma oxidized low-density lipoprotein (oxLDL), a marker of oxidative stress, and the prognosis of patients with chronic congestive heart failure (CHF).: BackgroundOxidative stress appears to play a role in the pathophysiology of CHF. We have recently reported the usefulness of plasma oxLDL as a marker of oxidative stress in CHF patients with dilated cardiomyopathy.: MethodsWe measured the plasma level of oxLDL by sandwich enzyme-linked immunosorbent assay using a specific monoclonal antibody against oxLDL in 18 age-matched normal subjects and in 84 patients with chronic CHF (New York Heart Association functional class II to IV) and monitored them prospectively for a mean follow-up period of 780 days.: ResultsPlasma oxLDL level was significantly higher in severe CHF patients than in control subjects and mild CHF patients. A significant negative correlation existed between the plasma level of oxLDL and left ventricular ejection fraction (LVEF) and a significant positive correlation between the plasma level of oxLDL and plasma norepinephrine level. Twenty-six patients had cardiac events; 14 had cardiac death and 12 were hospitalized for heart failure or other cardiovascular events. Among 10 variables including LVEF and neurohumoral factors, only high plasma levels of brain natriuretic peptide and oxLDL were shown to be independent predictors of mortality.: ConclusionsThese results indicate that the plasma level of oxLDL is a useful predictor of mortality in patients with CHF, suggesting that oxidative stress plays an important role in the pathophysiology of CHF. [Copyright &y& Elsevier]

: ObjectivesWe sought to develop a prognostic model to predict the disappearance of left atrial thrombi (LAT) among candidates for percutaneous transvenous mitral commissurotomy (PTMC).: BackgroundComplete LAT resolution can be achieved with oral anticoagulation, allowing a number of patients to safely undergo PTMC.: MethodsWe randomly allocated 108 PTMC candidates with LAT into two subsets—one to derive the model and the other to validate it. The existence of LAT and its size were measured by transesophageal echocardiography. Patients were given oral anticoagulation and followed up for 6 to 34 months. There was a 62% disappearance rate of LAT.: ResultsWe developed the following model: P = 1/(1 + exponential [−8.1 + 1.8 NYHA + 0.7 area]), where NYHA = New York Heart Association functional class (from I to IV), and area = LAT area (in cm2). The model was well calibrated (goodness-of-fit test, p = 0.82) and well discriminated (area under the receiver-operating characteristics [ROC] curve = 0.92). Performance in the validating sample was equally good (area under the ROC curve = 0.94; goodness-of-fit test, p = 0.16). When a cut-off point of p > 0.7 was used to designate the LAT disappearance in the validating set, the model had a sensitivity, specificity and positive and negative predictive values of 93.3%, 79.2%, 84.9% and 90.5%, respectively.: ConclusionsCombined clinical (NYHA functional class) and echocardiographic (LAT area) variables are predictive of the 34-month outcome of oral anticoagulation for LAT resolution among PTMC candidates. This simple and highly predictive model might be potentially useful for clinical assessment and proper management. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to determine whether nesiritide, administered for acute decompensated congestive heart failure (CHF), affects healthcare costs by hospital length of stay (LOS), readmissions and short-term mortality, compared to dobutamine.: BackgroundDobutamine is a commonly used inotropic treatment for CHF. Although dobutamine may have favorable hemodynamic and symptomatic effects, its use may be associated with side effects such as tachycardia, cardiac arrhythmias and myocardial ischemia. Nesiritide (B-type natriuretic peptide) is a new intravenous (IV) drug that produces hemodynamic and symptomatic improvement through balanced vasodilatory effects, neurohormonal suppression and enhanced natriuresis and diuresis.: MethodsFrom an open-label randomized study of nesiritide versus standard care (SC) in patients with CHF requiring hospitalization, we compared short-term outcome data from patients given nesiritide (0.015 or 0.03 μg/kg per min) with a subgroup of SC patients given dobutamine. A total of 261 patients are included in this analysis.: ResultsCompared to dobutamine, both nesiritide doses were administered for a shorter total duration (p < 0.001), and the total duration of all IV vasoactive therapy (including study drug) was also shorter (p ≤ 0.012). Although there was no difference in LOS, there was a trend toward decreased readmissions in the two nesiritide groups (8% and 11%, respectively, vs. 20% in the dobutamine group). Six-month mortality was lower in the nesiritide groups.: ConclusionsTreatment of decompensated CHF with nesiritide may lead to lower healthcare costs and reduced mortality compared to treatment with dobutamine. [Copyright &y& Elsevier]

: ObjectivesThe purpose of this study was to evaluate an implantable cardioverter-defibrillator (ICD) incorporating biventricular pacing.: BackgroundBiventricular pacing improves the symptoms of heart failure, a frequent problem in ICD recipients.: MethodsThis prospective multicenter study evaluated the safety and efficacy of an ICD with biventricular pacing.: ResultsA total of 84 patients with a standard ICD indication, symptomatic heart failure, left ventricular (LV) ejection fraction <35% and a QRS duration >130 ms were included in the trial. In 81 of 84 patients the LV lead was successfully implanted. Patients significantly improved in the 6-min hall-walk test (baseline 304 ± 131 m, three months 397 ± 142 m, p < 0.001), quality of life (baseline 38.9 ± 21.2, three months 26.5 ± 21.2, p < 0.001) and the New York Heart Association (NYHA) classification (baseline 2.8 ± 0.6, three months 2.2 ± 0.5). Left ventricular end-diastolic (from 79.6 ± 13.0 mm to 73.6 ± 12.9 mm, p = 0.002) and end-systolic (from 68.3 ± 13.5 mm to 63.9 ± 12.9 mm, p < 0.001) diameter decreased, and fractional shortening increased (from 16 ± 6% to 18 ± 6%, p = 0.018). Of the patients 26 experienced 472 episodes of spontaneous sustained ventricular tachyarrhythmias. All episodes were successfully terminated except for 16 episodes occurring in a patient with incessant ventricular tachycardia. Biventricular antitachycardia pacing was more effective than right ventricular antitachycardia pacing (p < 0.001). During follow-up (median 185 days, range 12 to 344 days) five patients died from progressive heart failure.: ConclusionsIncorporating biventricular pacing in an ICD is feasible and leads to an improvement of heart failure symptoms. Therefore, this therapy may become an option for patients who need ICD therapy in the presence of severe heart failure. [Copyright &y& Elsevier]

: ObjectivesThe purpose of this study was to determine the mechanism by which 60°C sauna treatment improves cardiac function in patients with chronic heart failure (CHF).: BackgroundWe have previously reported that repeated 60°C sauna treatment improves hemodynamic data and clinical symptoms in patients with CHF. We hypothesized that the sauna restores endothelial function and then improves cardiac function.: MethodsTwenty patients (62 ± 15 years) in New York Heart Association (NYHA) functional class II or III CHF were treated in a dry sauna at 60°C for 15 min and then kept on bed rest with a blanket for 30 min, daily for two weeks. Ten patients with CHF, matched for age, gender and NYHA functional class, were placed on a bed in a temperature-controlled (24°C) room for 45 min as the nontreated group. Using high-resolution ultrasound, we measured the diameter of the brachial artery at rest and during reactive hyperemia (percent flow-mediated dilation, %FMD: endothelium-dependent dilation), as well as after sublingual administration of nitroglycerin (%NTG: endothelium-independent dilation). Cardiac function was evaluated by measuring the concentrations of plasma brain natriuretic peptide (BNP).: ResultsClinical symptoms were improved in 17 of 20 patients after two weeks of sauna therapy. The %FMD after two-week sauna treatment significantly increased from the baseline value, whereas the %NTG-induced dilation did not. Concentrations of BNP after the two-week sauna treatment decreased significantly. In addition, there was a significant correlation between the change in %FMD and the percent improvement in BNP concentrations in the sauna-treated group. In contrast, none of the variables changed at the two-week interval in the nontreated group.: ConclusionsRepeated sauna treatment improves vascular endothelial function, resulting in an improvement in cardiac function and clinical symptoms. [Copyright &y& Elsevier]

: ObjectivesThe aim of this study was to describe long-term outcome in patients with apical hypertrophic cardiomyopathy (ApHCM) followed in a tertiary referral center.: BackgroundApical hypertrophic cardiomyopathy is a relatively rare form of hypertrophic cardiomyopathy (HCM), first described in Japan. Initial reports, based on a limited number of patients, emphasized the benign nature of this condition.: MethodsA retrospective study of 105 patients with ApHCM diagnosed at the Toronto General Hospital from 1975 to 2000 was performed. Symptoms, clinical findings, mortality and cardiovascular morbidity were analyzed.: ResultsThe mean age at presentation was 41.4 ± 14.5 years. During a mean follow-up of 13.6 ± 8.3 years from presentation, cardiovascular mortality was 1.9% (2/105) and annual cardiovascular mortality was 0.1%. Overall survival was 95% at 15 years. Thirty-two patients (30%) had one or more major morbid events, the most frequent being atrial fibrillation (12%) and myocardial infarction (10%). Probability of survival without morbid events was 74% at 15 years. Three predictors of cardiovascular morbidity were identified: age at presentation <41 years, left atrial enlargement, and New York Heart Association (NYHA) class ≥II at baseline. Forty-four percent of the patients were asymptomatic at the time of last follow-up.: ConclusionsApical hypertrophic cardiomyopathy in North American patients is not associated with sudden cardiac death and has a benign prognosis in terms of cardiovascular mortality. Nevertheless, one third of these patients experience serious cardiovascular complications, such as myocardial infarction and arrhythmias. These data are likely to influence the counseling and management of patients with ApHCM. [Copyright &y& Elsevier]

: ObjectivesThe goal of this study was to compare the efficacy of biventricular pacing (BIV) at the most delayed wall of the left ventricle (LV) and at other LV walls.: BackgroundBiventricular pacing could provide additional benefit when it is applied at the most delayed site.: MethodsIn 31 patients with advanced nonischemic heart failure, the activation delay was defined, in blind before BIV, by regional noninvasive Tissue Doppler Imaging as the time interval between the end of the A-wave (C point) and the beginning of the E-wave (O point) from the basal level of each wall. The left pacing site was considered concordant with the most delayed site when the lead was inserted at the wall with the greatest regional interval between C and O points (COR). After BIV, patients were divided into group A (13/31) (i.e., paced at the most delayed site) and group B (18/31) (i.e., paced at any other site).: ResultsAfter BIV, in all patients LV end-diastolic (LVEDV) and end-systolic (LVESV) volumes decreased (p = 0.025 and 0.001), LV ejection fraction (LVEF) increased (p = 0.002), QRS narrowed (p = 0.000), New York Heart Association class decreased (p = 0.006), 6-min walked distance (WD) increased (p = 0.046), the interval between closure and opening of mitral valve (CO) and isovolumic contraction time (ICT) decreased (p = 0.001 and 0.000), diastolic time (EA) and Q-P2 interval increased (p = 0.003 and 0.000), while Q-A2 interval and mean performance index (MPI) did not change. Group A showed greater improvement over group B in LVESV (p = 0.04), LVEF (p = 0.04), bicycle stress testing work (p = 0.03) and time (p = 0.08) capacity, CO (p = 0.04) and ICT (p = 0.02).: ConclusionsAfter BIV, LV performance improved significantly in all patients; however, the greatest improvement was found in patients paced at the most delayed site. [Copyright &y& Elsevier]

: ObjectivesWe sought to determine the effect of angiotensin receptor blockers (ARBs) on mortality and hospitalization in patients with heart failure (HF).: BackgroundThere is uncertainty regarding the efficacy of ARBs as substitute or adjunctive therapy to angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of HF.: MethodsWe conducted a meta-analysis of all randomized controlled trials that compared ARBs with either placebo or ACEIs in patients with symptomatic HF. The pooled outcomes were all-cause mortality and hospitalization for HF.: ResultsSeventeen trials involving 12,469 patients were included. Overall, ARBs were not superior to controls in the pooled rates of death (odds ratio: 0.96; 95% confidence interval: 0.75 to 1.23) or hospitalization (0.86; 0.69 to 1.06). Stratified analysis, however, showed a non-significant trend in benefit of ARBs over placebo in reducing mortality (0.68; 0.38 to 1.22) and hospitalization (0.67; 0.29 to 1.51) when given in the absence of background ACEI therapy. When compared directly with ACEIs, ARBs were not superior in reducing either mortality (1.09; 0.92 to 1.29) or hospitalization (0.95; 0.80 to 1.13). In contrast, the combination therapy of ARBs and ACEIs was superior to ACEIs alone in reducing hospitalization (0.74; 0.64 to 0.86) but not mortality (1.04; 0.91 to 1.20).: ConclusionsThis meta-analysis cannot confirm that ARBs are superior in reducing all-cause mortality or HF hospitalization in patients with symptomatic HF, particularly when compared with ACEIs. However, the use of ARBs as monotherapy in the absence of ACEIs or as combination therapy with ACEIs appears promising. [Copyright &y& Elsevier]

: ObjectivesWe sought to determine whether a multidisciplinary outpatient management program decreases chronic heart failure (CHF) hospital readmissions and mortality over a six-month period.: BackgroundHospital admission for CHF is an important problem amenable to improved outpatient management.: MethodsTwo hundred patients hospitalized with CHF at increased risk of hospital readmission were randomized to a multidisciplinary program or usual care. A study cardiologist and a CHF nurse evaluated each patient and made recommendations to the patient’s primary physician before randomization. The intervention team consisted of a cardiologist, a CHF nurse, a telephone nurse coordinator and the patient’s primary physician. Contact with the patient was on a prespecified schedule. The CHF nurse followed an algorithm to adjust medications. Patients in the nonintervention group were followed as usual. The primary outcome was the composite of the number of CHF hospital admissions and deaths over six months, compared by using a log transformation t test by intention-to-treat analysis.: ResultsThe median age of the study patients was 63.5 years, and 39.5% were women. There were 43 CHF hospital admissions and 7 deaths in the intervention group, as compared with 59 CHF hospital admissions and 13 deaths in the nonintervention group (p = 0.09). The quality-of-life score, percentage of patients on target vasodilator therapy and percentage of patients compliant with diet recommendations were significantly better in the intervention group. Cost per patient, in 1998 U.S. dollars, was similar in both groups.: ConclusionsThis study demonstrates that a six-month, multidisciplinary approach to CHF management can improve important clinical outcomes at a similar cost in recently hospitalized high-risk patients with CHF. [Copyright &y& Elsevier]

: ObjectivesWe sought to analyze whether a microcirculatory dysfunction might be associated with isolated ventricular noncompaction (IVNC).: BackgroundIn IVNC, which is a cardiomyopathy thus far “unclassified” by the World Health Organization, heart failure and sudden cardiac death are common findings, but the pathophysiologic mechanisms are unknown.: MethodsIn 12 patients with IVNC and 14 control subjects, quantitative evaluation of regional myocardial perfusion (myocardial blood flow [MBF]) and coronary flow reserve (CFR, hyperemic/baseline MBF) was performed using positron emission tomography and 13N-ammonia. The left ventricular myocardium was divided into nine segments, and the two-dimensional echocardiogram in each patient with IVNC was compared with CFR in each segment. Noncompaction was defined as a two-layered structure with excessive trabeculation.: ResultsThe CFR in control subjects averaged 4.2 ± 0.9, providing a cut-off value ≥2.5, but it was 2.1 ± 0.8 in patients with IVNC. A perfusion scan defect was found in 14 of 24 segments with noncompaction, although no defect was found in 76 of 84 normal segments (overall agreement 83%, p < 0.0001 by the chi-square test). In 16 of 21 segments with noncompaction, a decreased CFR was found; but a decreased CFR was also found in 36 of 60 segments without noncompaction (p = NS). In 45 of the 57 segments with wall motion abnormalities, CFR was decreased, but it was preserved in 17 of the 24 segments with normal wall motion (agreement 77%, p < 0.0001).: ConclusionsIn patients with IVNC, a decreased CFR is not confined to noncompacted segments, but extends to most segments with wall motion abnormalities. Thus, coronary microcirculatory dysfunction is associated with IVNC. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to determine predictors of restenosis after successful percutaneous mitral commissurotomy (PMC) and its relationship to late clinical outcome.: BackgroundThe restenosis rate after PMC and its relationship to late clinical outcome is poorly defined.: MethodsSerial echocardiography was performed in 310 patients who underwent PMC. Restenosis, defined as mitral valve area (MVA) <1.5 cm2 and ≥50% loss of initial MVA increase, was determined by both two-dimensional (2D) and Doppler echocardiography. Clinical, echocardiographic and cardiac catheterization variables were evaluated to determine predictors of restenosis. The relationship between restenosis and major adverse clinical events (death, repeat PMC or mitral valve replacement) and functional status was assessed.: ResultsAcute procedural success occurred in 206 patients (66%), who were then followed for restenosis. The cumulative restenosis rate was approximately 40% at six years after successful PMC (44% by 2D and 40% by Doppler MVA). The only independent predictor of restenosis was echocardiographic score (restenosis at five years was 20% for score <8 vs. 61% for score ≥8, p < 0.001). The decline in MVA and occurrence of restenosis was gradual and progressive during the follow-up period. Procedural results and baseline factors predicted event-free survival. Restenosis by 2D MVA was related to adverse events or New York Heart Association functional class 3 to 4 symptoms, but restenosis was not an independent predictor of clinical outcome by multivariate analysis.: ConclusionsRestenosis is a common, gradual and progressive occurrence after successful PMC and is predicted by higher echocardiographic score. Restenosis is related to late adverse clinical outcome, though clinical outcome remains best predicted by the acute procedural results of PMC. [Copyright &y& Elsevier]

: ObjectivesWe sought to assess the occurrence and clinical significance of stroke and peripheral arterial embolizations at non-central nervous system sites in a large, community-based cohort with hypertrophic cardiomyopathy (HCM).: BackgroundSuch vascular events are insufficiently appreciated complications of HCM for which there is limited information on occurrence, clinical profile and determinants.: MethodsWe assessed the clinical features of patients with stroke and other peripheral vascular events in a consecutive group of patients with HCM from four regional cohorts not subject to significant tertiary referral bias.: ResultsOf the 900 patients, 51 (6%) patients experienced stroke or other vascular events over 7 ± 7 years, including 44 patients with stroke; 21 (41%) of these 51 patients died or were permanently disabled. The overall incidence was 0.8%/year and 1.9% for patients >60 years old. Age at first event ranged from 29 to 86 years (mean 61 ± 14 years). Most (n = 37; 72%) events occurred in those >50 years, although 14 (28%) younger patients (≤50 years) also had events. Multivariate analysis showed stroke and other peripheral vascular events to be independently associated with congestive symptoms and advanced age, as well as with atrial fibrillation (in 45 [88%] of 51 patients), at the initial evaluation. The cumulative incidence of these events among patients with atrial fibrillation was significantly higher in non-anticoagulated patients as compared with patients receiving warfarin (31% vs. 18%; p < 0.05).: ConclusionsStroke and peripheral embolizations showed a 6% prevalence rate and an incidence of 0.8%/year in a large, unselected HCM group. These profound complications of HCM, which may lead to disability and death, were substantially more common in the elderly, occurred almost exclusively in patients with paroxysmal or chronic atrial fibrillation and appeared to be reduced in frequency by anticoagulation. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to compare the three-year survival after percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) in physician-directed and patient-choice registries with the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial results.: BackgroundThe AWESOME multicenter randomized trial and registry compared the long-term survival after PCI and CABG for the treatment of patients with medically refractory myocardial ischemia and at least one additional risk factor for adverse outcome with CABG. The randomized trial demonstrated comparable three-year survival.: MethodsOver a five-year period (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior heart surgery, myocardial infarction within seven days, left ventricular ejection fraction <0.35, age >70 years, intra-aortic balloon required to stabilize) were identified. By physician consensus, 1,650 patients formed a physician-directed registry assigned to CABG (692), PCI (651) or further medical therapy (307), and 781 were angiographically eligible for random allocation; 454 of these patients constitute the randomized trial, and the remaining 327 constitute a patient choice registry. Survival for CABG and PCI was compared using Kaplan-Meier curves and log-rank tests.: ResultsThe CABG and PCI 36-month survival rates for randomized patients were 79% and 80%, respectively. The CABG and PCI 36-month survival rates were both 76% for the physician-directed subgroup; comparable survival rates for the patient-choice subgroup were 80% and 89%, respectively. None of the global log-rank tests for survival demonstrated significant differences.: ConclusionsBoth registries support the randomized trial conclusion: PCI is an alternative to CABG for some medically refractory high-risk patients. [Copyright &y& Elsevier]

Left or biventricular (BiV) pacing, or cardiac resynchronization therapy, was proposed nearly 10 years ago as an adjunctive treatment for patients with advanced heart failure (HF) complicated by discoordinate contraction due to intraventricular conduction delay. Since then, both short-term and a growing number of long-term clinical trials have reported on the mechanisms and short- and mid-term efficacy of this approach, with encouraging results. Therapy is implemented with novel pacing systems incorporating an endocardial lead to stimulate the lateral free wall via a cardiac vein, and often a right ventricular (RV) apex lead to provide BiV stimulation. A third atrial sensing lead monitors intrinsic rhythm and provides timing data to ensure ventricular pre-excitation. Modulation of the electronic atrial-ventricular (AV) time delay can optimize contractile synchrony, enhance the contribution of atrial systole, and reduce mitral regurgitation. Individuals with advanced HF, a wide QRS complex often with an AV time delay, and evidence of contraction dyssynchrony in viable myocardium represent the target patient group. Short-term studies reveal systolic augmentation and chamber efficiency from pacing resynchronization that can be substantial. Long-term studies reveal improved symptoms and exercise capacity, and some report reversal of chronic cardiac dilation. However, important questions regarding long-term efficacy and mortality impact, optimal mode for pacing stimulation, and role of combined pacing/cardioverter/defibrillation devices remain unresolved. Here we review pathophysiologic mechanisms, short- and long-term clinical results, and future directions of this new and promising therapy. [Copyright &y& Elsevier]

: ObjectivesWe sought to evaluate the association between the extent of coronary artery disease (CAD) and survival in patients with symptomatic heart failure (HF) and to create the most prognostically powerful clinical definition of ischemic cardiomyopathy.: BackgroundAn ischemic etiology of HF is known to be a predictor of adverse outcome; however, there is no uniform definition for ischemic cardiomyopathy.: MethodsWe assessed the clinical history and coronary anatomy of patients with symptomatic HF and ejection fraction ≤40% undergoing diagnostic coronary angiography between 1986 and 1999 (n = 1,921). Five classification schemes were tested to identify the most prognostically powerful method for defining the extent of CAD and to develop the best definition of ischemic cardiomyopathy for prognostic purposes.: ResultsA more extensive CAD was independently associated with shorter survival. When the various classification schemes were compared, a modified number-of-diseased-vessels classification, in which patients with single-vessel disease and no prior history of revascularization or myocardial infarction (MI) were classified as nonischemic, provided the most prognostic power. A definition of ischemic cardiomyopathy that incorporated this definition had more prognostic power than the traditional definition.: ConclusionsAngiographically diagnosed ischemic HF is associated with shorter survival than nonischemic HF. A more extensive CAD is independently associated with shorter survival, and patients with single-vessel disease and no history of MI or revascularization should be classified as nonischemic for prognostic purposes. Standardization of the definition of ischemic cardiomyopathy will be useful in the conduct and interpretation of clinical research in HF. [Copyright &y& Elsevier]

: ObjectivesWe sought to compare the neurohormonal responses and clinical effects of long-term, high-dose versus low-dose enalapril in patients with chronic heart failure (CHF).: BackgroundExamination of neurohormonal and clinical responses in patients receiving different doses of angiotensin-converting enzyme (ACE) inhibitors may provide insight into the potential for additional suppression with angiotensin II (AT-II) or aldosterone antagonists.: MethodsSeventy-five patients with CHF were randomized to receive either high-dose (40 mg/day, n = 37) or low-dose (5 mg/day, n = 38) enalapril over six months. The results from exercise testing, echocardiography, tissue-specific ACE activity and monthly pre- and post-enalapril neurohormonal levels were compared.: ResultsDespite greater intra-group improvements in plasma renin activity and serum aldosterone levels in the high-dose group, no statistically significant differences were observed between the two groups in all variables, except for serum ACE activity at the end of study. Elevated serum aldosterone and plasma AT-II levels were observed in 35% and 85% of patients, respectively, at 34 weeks, an inter-group difference that was not statistically significant. A trend toward higher levels of tissue-specific ACE activity in the high-dose group compared with the low-dose group at the end of study was observed (p = 0.054). A predefined composite end point of clinical events had a trend toward better improvement in the high-dose group.: ConclusionsThis study could not demonstrate a difference between high- and low-dose enalapril in terms of serum aldosterone and plasma AT-II suppression, despite a dose-dependent reduction in serum ACE activity. Even at maximal doses of enalapril, elevated serum aldosterone and plasma AT-II levels were frequently observed. [Copyright &y& Elsevier]

: ObjectivesThe purpose of this study was to create an automated surveillance tool for reporting the incidence, prevalence and processes of care for patients with heart failure.: BackgroundPrevious epidemiologic studies suggest that the increasing prevalence of heart failure is a consequence of improved survival coupled with minimal changes in disease prevention. Developing new, efficient methods of assessing the incidence and prevalence of heart failure could allow continued surveillance of these rates during an era of rapidly changing treatments and health care delivery patterns.: MethodsUsing administrative data sets, we created a definition of heart failure using diagnosis codes. After adjustment for patients leaving our health system or death, we derived the incidence, prevalence and mortality of the population with heart failure from 1989 to 1999.: ResultsA total of 29,686 patients of all ages, 52.6% women and 47.4% men, met the definition of heart failure. Mean ages were 71.1 ± 14.5 for women and 67.7 ± 14.4 for men, p < 0.0001. Race proportions were 50.5% white, 44.6% African American and 4.9% other race. Incidence rates were higher in men and African Americans across all age groups. There was an annual increase in prevalence of 1/1,000 for women and 0.9/1,000 for men, p = 0.001 for both trends.: ConclusionsThrough the feasible and valid use of automated data, we have confirmed a chronic disease epidemic of heart failure manifested primarily by an increase in prevalence over the past decade. Our surveillance system mirrors the results of epidemiologic studies and may be a valid method for monitoring the impact of prevention and treatment programs. [Copyright &y& Elsevier]

: ObjectivesThe goal of this study was to test the hypothesis that growth hormone (GH) administration to patients with chronic heart failure (CHF) corrects their vascular dysfunction.: BackgroundEndothelial dysfunction is a prominent feature of CHF. Recent evidence indicates that GH plays a role in vascular reactivity.: MethodsWe studied vascular reactivity in 16 patients with CHF (New York Heart Association class II to III) before and after three months of GH (4 IU subcutaneously every other day) or placebo administration in a randomized, double-blind trial. We measured forearm blood flow (FBF) by strain-gauge plethysmography during intrabrachial, graded infusion of acetylcholine (ACh) and sodium nitroprusside (NP). We also measured the forearm balance of nitrite and cyclic guanosine monophosphate (cGMP) before and during ACh infusion. Maximal oxygen uptake (VO2max) was measured by breath-to-breath respiratory gas analysis.: ResultsBefore treatment, the response of FBF to ACh was flat (p = NS). Growth hormone, but not placebo, greatly improved this response (p = 0.03) and, concomitantly, increased the forearm release of nitrite and cGMP (p < 0.05). Growth hormone also potentiated the FBF response to NP (p = 0.013). Growth hormone interacted with ACh response (p = 0.01) but not with the response to NP (p = NS). Accordingly, GH enhanced the slope of the dose-response curve to ACh (p < 0.05) but not to NP. The VO2max increased significantly after GH treatment (20 ± 2 and 26 ± 2 ml ·Kg−1· min−1 before and after GH treatment, respectively, p < 0.05) but not after placebo.: ConclusionsA three-month treatment with GH corrected endothelial dysfunction and improved non-endothelium-dependent vasodilation in patients with CHF. The data highlight the potential role of GH in the progression of congestive heart failure. [Copyright &y& Elsevier]

A blood test that would aid in the diagnosis and management of patients with congestive heart failure would have a favorable impact on the staggering costs of the disease. B-type naturetic peptide (BNP) is synthesized, in the cardiac ventricles and its release is directly proportional to ventricular volume expansion and pressure overload. Levels of BNP correlate with left ventricular pressure, amount of dyspnea, and the state of neurohumoral modulation. BNP also correlates closely with New York Heart Association classification. A cut point of 100 pg/mL appears to discriminate patients with congestive heart failure from those without congestive heart failure. Measurement of BNP may also be an excellent screening tool for LV dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: To our knowledge, no study has addressed the relationship between adherence to a Mediterranean diet style and severity of heart failure. The aim of this retrospective study was to evaluate the relationship between adherence to the Mediterranean diet assessed using the calculation of Mediterranean diet score and congestive heart failure (CHF), its severity, and pathogenesis., Methods: We analyzed charts and collected data of all consecutive patients with a diagnosis of CHF at admission to our Internal Medicine Ward from 2008 to 2014., Results: We analyzed 209 patients with CHF and 200 controls. Patients with CHF showed a significantly lower mean MeDi score than controls. At receiver operating characteristic curve analysis, we found a good sensitivity and specificity of mean MeDi score to predict CHF. We also observed a significant positive correlation between MeDi score and ischemic pathogenesis of CHF, a positive relationship between New York Heart Association (NYHA) class and ischemic heart disease, and a significant negative relationship between NYHA class and MeDi score., Conclusion: The beneficial effects of adherence to the Mediterranean diet suggest a possible answer to the question of the biochemical bases of our data, which should be seen as the direct consequence of the anti-inflammatory, antioxidant, and anti-remodeling effects linked to the diet., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Adenosine is known to be an endogenous cardioprotective substance. Since we have reported that adenosine levels increase in patients with chronic heart failure, we tested whether further elevation of the adenosine levels due to dipyridamole or dilazep for 6 months modulates the pathophysiology of chronic heart failure. In patients with chronic heart failure, either dipyridamole (300 mg/d n = 17) or dilazep (300 mg/d n = 5) were administered for 6 months. Twenty-two patients (mean ± SE age 58 ± 4 years old) attending a specialized chronic heart failure (CHF) clinic over 6 months and judged as in New York Heart Association (NYHA) function class II or III were examined. The other drugs used for the treatment of CHF were not altered during the study. There were 5 patients with CHF caused by ischemic heart diseases, and 17 patients with either valvular heart diseases or dilated cardiomyopathy. We found that increases in the plasma adenosine levels (202 ± 34 and 372 ± 74) nmol/L before and after dipyridamole administration, P < 0.005 ameliorate the severity of CHF (NYHA: 2.1 ± 0.5 to 1.7 ± 0.2). Both ejection fraction and maximal oxygen consumption increased. These improvements in the severity of chronic heart failure returned to baseline levels 6 months after discontinuation of dipyridamole. Comparable results were obtained in the dilazep protocol. We suggest that the elevation of plasma adenosine levels improves the pathophysiology of CHF. [ABSTRACT FROM AUTHOR]

Background: Fragmented QRS (fQRS) complex is an electrocardiographic pattern which reflects myocardial scarring. We aimed to investigate the relationship between the presence of fragmented QRS (fQRS) on electrocardiogram (ECG) and plasma galectin-3 levels in patients with heart failure (HF) and severely decreased left ventricular ejection fraction (LVEF ≤ 35%).Methods: We prospectively enrolled 125 symptomatic HF patients (NYHA class II-III) with severely reduced LVEF (≤35%). fQRS was identified in ECG. Galectin-3 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured. Patients were divided into two groups based on the presence (n = 40) or absence (n = 85) of a fQRS on ECG.Results: Majority of patients were male (87.70%), and mean age was 65.1 ± 11.6. Galectin-3 and NT-proBNP levels were found to be significantly higher in the fQRS (+) group compared with the fQRS (-) group (NT-proBNP 5,362 ± 701 pg/ml vs. 4,452 ± 698 pg/ml; p < 0.001, galectin-3 607 ± 89.8 pg/ml vs. 509.4 ± 63.5 pg/ml; p < 0.001). Multivariate analyses revealed galectin-3 and NT-proBNP levels are the presence of fQRS on ECG (p < 0.001 and p < 0.001, respectively). The area under the curve using the galectin-3 level for fQRS was 0.819.Conclusions: fQRS and serum galectin-3 levels are associated with myocardial fibrosis and are associated with poor prognosis in heart failure. In our study, a positive correlation was found between serum galectin-3 levels and fQRS on ECG. [ABSTRACT FROM AUTHOR]

This study aimed that we were classification of physical activity in patients with heart failure categorized as New York Heart Association (NYHA) class I or II. We were a survey using a researcher- administered questionnaire, SF-8, the Specific Activity Scale (SAS), and the Scale to Measure Self-Care Behavior of Patients with Heart Disease. We included 70 patients who were treated in the Department of Cardiovascular Medicine at Hospital A. Regarding patient characteristics and clinical information after the cluster analysis, there were significant differences in the NYHA class (p = 0.001), BNP level (p = 0.012), self-management of medication adherence (p = 0.000), and exercise habits (p = 0.005). We summarized characteristics of each group as follows : Group A showed high tolerance to physical activity and near-perfect self-management; Group B showed moderate tolerance to physical activity but was not willing to commit to daily exercise and self-management; and Group C showed low tolerance to physical activity and often requested others to handle medication management. We needed that tolerance to physical activity and proposals for tailored instruction according to patient conditions, and needed that instructions tailored to the characteristics of heart failure patients in groups A-C. J. Med. Invest. 67 : 124-133, February, 2020.