Incidence Of Congestive Heart Failure Research Articles

Vitamin E use and congestive heart failure in the cardiovascular health study

In the Cardiovascular Health Study, a population-based, longitudinal study of coronary heart disease and stroke in adults 65 years and older, we examined the association of vitamin E use with incident hospitalization for congestive heart failure (CHF) and of committee-adjudicated CHF over an average of 8.3 years. Vitamin E use was assessed by prescription or over-the-counter medications presented or self-reported use at eight annual contacts beginning in 1992. Those with any history of CHF, or no assessment of vitamin E use, were excluded from the analyses. In time-dependent Cox regression analyses (N=3569, 1211 events) adjusted for age, gender and race, vitamin E use was not significantly associated with the combined outcome of incident CHF or hospitalization for CHF [Hazard Ratio (HR)=0.87, 95% Confidence Interval (CI)=0.75, 1.01]. Adjustment for CHF risk factors and potential confounders did not appreciably alter this association. When adjusted for age, gender and race vitamin E use was significantly inversely associated with first hospitalization for CHF (1082 events, HR=0.78, 95%CI=0.67, 0.91), but was no longer significant after adjustment for CHF risk factors (HR=0.86, 95%CI=0.73, 1.01). These results do not support the reported association of vitamin E use with increased risk for CHF as reported in recent randomized trials (HOPE TOO and GISSI Prevenzione). Funded by: Pharmavite LLC.

Letter by Bleiziffer et al Regarding Article, “Long-Term Outcomes After Valve Replacement for Low-Gradient Aortic Stenosis: Impact of Prosthesis-Patient Mismatch”

To the Editor: With great interest, we read the article by Kulik and associates1 identifying patient-prosthesis mismatch (PPM) (defined as an effective orifice area [EOA] index below 0.85 cm2/m2) as an independent predictor of a higher incidence of congestive heart failure and impaired left ventricular mass regression after aortic valve replacement in patients with low-gradient aortic stenosis. In the study by Kulik et al, PPM was assessed by reference tables, although echocardiographic EOA index data …

Diurnal Blood Pressure Pattern and Risk of Congestive Heart Failure

Context. High blood pressure (BP) is the most important risk factor for congestive heart failure (CHF) at a population level, but the relationship of an altered diurnal BP pattern to the risk of subsequent CHF is unknown. Objectives. To explore 24-hour ambulatory BP characteristics as predictors of CHF incidence and to investigate whether altered diurnal BP patterns confer any additional risk information beyond that provided by conventional office BP measurements. Design, Setting, and Participants. Prospective, community-based, observational cohort in Uppsala, Sweden, including 951 elderly men free of CHF, valvular disease, and left ventricular hypertrophy at baseline between 1990 and 1995, followed until the end of 2002. Twenty-four-hour ambulatory BP monitoring was performed at baseline, and the BP variables were analyzed as predictors of subsequent CHF. The main outcome measure was first hospitalization for CHF. Results. Seventy men developed CHF during follow-up, with an incidence rate of 8.6 per 1000 person-years at risk. In multivariable Cox proportional hazards models adjusted for antihypertensive treatment and established risk factors for CHF (myocardial infarction, diabetes, smoking, body mass index, and serum cholesterol level), a 1-SD (9-mm Hg) increase in nighttime ambulatory diastolic BP (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.02–1.55) and the presence of “nondipping” BP (night-day ambulatory BP ratio ≥1; HR, 2.29; 95% CI, 1.16–4.52) were associated with an increased risk of CHF. After adjusting for office-measured systolic and diastolic Bps, nondipping BP remained a significant predictor of CHF (HR, 2.21; 95% CI, 1.12–4.36 vs normal night-day pattern). Nighttime ambulatory diastolic BP and nondipping BP were also significant predictors of CHF after exclusion of all participants who had an acute myocardial infarction before baseline or during follow-up. Conclusions. Nighttime BP appears to convey additional risk information about CHF beyond office-measured BP and other established risk factors for CHF. The clinical value of this association remains to be established in future studies.—Ingelsson E, Bjorklund-Bodegard K, Lind L, et al. Diurnal blood pressure pattern and risk of congestive heart failure. JAMA. 2006;295:2859–2866. Comment. Ambulatory BP monitoring provides information that is not obtained from conventional office-based BP measurement, such as mean BP over a 24-hour period and circadian BP patterns. Staessen et al1demonstrated that a nondipping pattern of BP (night-day ambulatory BP ratio ≥1) and nighttime BP more accurately predicted cardiovascular events than daytime BP. A reduced circadian BP variation is a common finding in CHF patients. The association of diastolic dysfunction with increased diastolic BP and nondipping in patients with hypertension and type 2 diabetes is also known. The primary aim of this study was to determine what characteristics of the 24-hour ambulatory BP measurements best predicted new-onset CHF, and how these characteristics of the 24-hour ambulatory BP measurements compared with office measurements. The prospective, community-based, observational cohort included 951 elderly men free of CHF, valvular disease, and left ventricular hypertrophy at baseline followed for a median of 9.1 years. Twenty-four-hour ambulatory BP monitoring along with office-based BP measurements were performed at baseline, and the BP variables, including nondipping pattern, were analyzed as predictors of subsequent CHF. Seventy men developed CHF during follow-up, with an incidence rate of 8.6 per 1000 person-years at risk. After adjusting for antihypertensive treatment and established risk factors for CHF (myocardial infarction, diabetes, smoking, body mass index, and serum cholesterol level), a 1-SD (9-mm Hg) increase in nighttime ambulatory diastolic BP and the presence of nondipping BP were associated with an increased absolute risk of CHF. A 5-mm Hg increment in nighttime ambulatory diastolic BP was associated with a 13%–25% increased risk of CHF. After adjusting for office-measured systolic and diastolic Bps, nondipping pattern remained a significant predictor of CHF. The incidence of CHF was 15 cases higher per 1000 person-years at risk for those with nondipping vs normal night—day BP pattern. Nighttime ambulatory diastolic BP and nondipping BP were also significant predictors of CHF even after exclusion of all participants who had an acute myocardial infarction before baseline or during follow-up. The few limitations of this study include limited generalizability to women and other age or ethnic groups, inadvertent exclusion of nonhospitalized patients with mild CHF, and unknown impact of BP pattern on systolic vs diastolic HF. The pathophysiologic mechanism behind this association is not yet clear, but the authors speculate that endothelial dysfunction and/or increased sympathetic activity may be dysfunctions playing significant roles. Reversed circadian BP pattern (nondipping) may be important per se or may be an indicator of an important trait like sleep apnea. Previous studies have shown an association of nondipping nocturnal Bps and ambulatory BP readings with both cardiovascular disease incidence and left ventricular hypertrophy, and these findings with regard to CHF are consistent. The authors are rightfully cautious about the clinical implications of these findings, but they may provide additional clues to understanding the progression from hypertension to CHF.

Congestive Heart Failure Is a Rare Event in Patients (pts) Receiving Imatinib Therapy.

Background: A recent report suggested that imatinib is cardiotoxic and can lead to severe left ventricular dysfunction and heart failure.Study Aim: To evaluate the incidence of congestive heart failure (CHF) in pts receiving imatinib.Methods: We reviewed all Grade III and IV cardiac or what could be considered cardiac-related adverse events (eg, shortness of breath, dyspnea on exertion, edema, etc) occurring in pts on clinical trials at MDACC involving imatinib.Results: 1276 pts were enrolled on clinical trials with imatinib from 7/28/1998 to 7/27/2006. After reviewing all reported adverse events, particularly those that could be considered of at least possible cardiac origin, 22 pts (1.8%) were identified as having symptoms that could be attributed to CHF. The median age for these 22 pts was 70 yrs (range, 49 to 83 yrs); 12 were male. Their diagnosis at the time of imatinib was started was chronic myeloid leukemia in chronic phase (11 of 561 pts, 1.96%), accelerated phase (4 of 384 pts, 1.04%), or blast phase (2 of 123 pt, 1.62%), myeloproliferative disorder (4 of 124 pts, 3.2%), acute lymphoblastic leukemia (1 of 74 pts, 1.35%) and none in 10 pts with c-kit positive AML. Twelve pts (55%) had received prior interferon therapy and 3 pts had received anthracyclins. The median time from start of imatinib therapy to a cardiac adverse event was 162 days (2–2045 days). Imatinib dose at the time of AE was 300mg/d in 1 pt, 400mg/d in 8 pts, 600mg/d in 9 pts, and 800mg/d in 5 pts. At the time these events were reported, 8 were considered possibly or probably related to imatinib. Eighteen pts had previous medical conditions predisposing to cardiac disease: CHF (6 pts, 27%), DM (6 pts, 27%), hypertension (10 pts, 45%), coronary artery disease (CAD) (8 pts, 36%), arrhythmia (3 pts, 14%) and cardiomyopathy (1 pt 5%). Fifteen pts had an echocardiogram or MUGA scan at the time of the event, and 9 of them had documented low ejection fractions (<50%); in only 2 of these 9 pts was there an echocardiogram prior to imatinib (LVEF >50% in both). Of the 9 pts with low ejection fractions at the time of the event , 6 had prior cardiac conditions (3 CAD, 2 CHF and 1 cardiomyopathy), one patient's low EF etiology could not be determined as no further cardiac evaluation was performed because of progressive disease, and one pt was on anagrelide prior to the event. Eleven of the 22 pts continued imatinib therapy with dose adjustments and management for the CHF symptoms with no further complications.Conclusions: Imatinib therapy as a causal factor of CHF is uncommon and is mainly seen in elderly patients with pre-existing cardiac conditions. Patients with a previous cardiac history should be monitored closely and treated aggressively with diuretics if they develop fluid retention.

Incidence of heart failure in infarcted rats that die spontaneously

The present study reports for the first time the incidence of congestive heart failure (CHF) in previously infarcted rats that died spontaneously. Previously, pulmonary (PWC) and hepatic (HWC) water contents were determined in normal rats: 14 control animals were evaluated immediately after sacrifice, 8 placed in a refrigerator for 24 h, and 10 left at room temperature for 24 h. In the infarcted group, 9 rats died before (acute) and 28 died 48 h after (chronic) myocardial infarction. Thirteen chronic animals were submitted only to autopsy (N = 13), whereas PWC and HWC were also determined in the others (N = 15). Seven rats survived 48 h and died during anesthesia. Notably, PWC differed in normal rats: ambient (75.7 ± 1.3%) < control (77.5 ± 0.7%) < refrigerator (79.1 ± 1.4%) and there were no differences with respect to HWC. No clinical signs of CHF (dyspnea, lethargy or foot edema) were observed in infarcted rats before death. PWC was elevated in all chronic and anesthetized rats. HWC was increased in 48% of chronic and in all anesthetized rats. Our data showed that PWC needs to be evaluated before 24 h post mortem and that CHF is the rule in chronic infarcted rats suffering natural death. The congestive syndrome cannot be diagnosed correctly in rats by clinical signs alone, as previously proposed.

Adjuvant Trastuzumab: A Milestone in the Treatment of HER-2-Positive Early Breast Cancer

Up to one fourth of women diagnosed with early breast cancer (EBC) have tumors that are human epidermal growth factor receptor 2 (HER-2) positive. This is associated with a high risk of relapse and death from meta-static disease. Trastuzumab, a monoclonal antibody directed against the extracellular domain of HER-2, improves survival and quality of life in women with HER-2-positive metastatic breast cancer receiving chemotherapy. Four major adjuvant trials-Herceptin Adjuvant (HERA), National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group (NCCTG) N9831, and Breast Cancer International Research Group (BCIRG) 006-including between them >13,000 women with HER-2-positive EBC, have investigated different adjuvant treatment approaches with trastuzumab. These trials have shown that trastuzumab reduces the 3-year risk of recurrence by about half in this population. The benefit was similar across the trials despite differences in patient populations, chemotherapy regimens, and sequencing of treatment. At a 2-year follow-up, interim results from the combined analysis of the NSABP B-31 and NCCTG N9831 trials showed a one third lower mortality for trastuzumab, and there was a trend toward an overall survival benefit in the HERA and BCIRG trials. A small Finnish trial, FinHer, investigating another regimen of trastuzumab, has also shown similarly positive results. Further follow-up of the major adjuvant trials will clarify the survival benefit for women receiving trastuzumab, as well as the optimal treatment duration (1 or 2 years). Notably, cardiac events in the trastuzumab-containing arms of these trials have remained within acceptable levels, with a slightly higher (0.6%-3.3%) incidence of congestive heart failure that mostly responded to treatment. Further follow-up will provide information on long-term cardiac safety. Overall, results from clinical trials are sufficiently compelling to consider 1 year of adjuvant trastuzumab treatment for women with HER-2-positive EBC based on the risk:benefit ratio demonstrated in these studies.

Incidence of heart failure in infarcted rats that die spontaneously

The present study reports for the first time the incidence of congestive heart failure (CHF) in previously infarcted rats that died spontaneously. Previously, pulmonary (PWC) and hepatic (HWC) water contents were determined in normal rats: 14 control animals were evaluated immediately after sacrifice, 8 placed in a refrigerator for 24 h, and 10 left at room temperature for 24 h. In the infarcted group, 9 rats died before (acute) and 28 died 48 h after (chronic) myocardial infarction. Thirteen chronic animals were submitted only to autopsy (N = 13), whereas PWC and HWC were also determined in the others (N = 15). Seven rats survived 48 h and died during anesthesia. Notably, PWC differed in normal rats: ambient (75.7 +/- 1.3%) < control (77.5 +/- 0.7%) < refrigerator (79.1 +/- 1.4%) and there were no differences with respect to HWC. No clinical signs of CHF (dyspnea, lethargy or foot edema) were observed in infarcted rats before death. PWC was elevated in all chronic and anesthetized rats. HWC was increased in 48% of chronic and in all anesthetized rats. Our data showed that PWC needs to be evaluated before 24 h post mortem and that CHF is the rule in chronic infarcted rats suffering natural death. The congestive syndrome cannot be diagnosed correctly in rats by clinical signs alone, as previously proposed.

Effects of early angiotensin-converting enzyme inhibition in patients with non–ST-elevation acute anterior myocardial infarction

No data are available on the clinical efficacy of the early administration (<24 hours from onset of chest pain) of angiotensin-converting enzyme inhibitors in non-thrombolysed patients with non-ST-elevation myocardial infarction (NSTEMI). We have addressed this issue in a subgroup of NSTEMI patients enrolled in the SMILE trial. Of the overall population of 1556 patients, 526 (33.8%) had an anterior wall NSTEMI, defined as an ST elevation <1 mm or an ST depression in at least two contiguous precordial leads with or without new abnormal Q waves. No patient of the SMILE Study received thrombolytic therapy or was reperfused. Patients were randomized, double-blind, to zofenopril (n = 253) or placebo (n = 273) for 6 weeks. The primary end point was the effect of treatment on the 6-week combined occurrence of death and severe congestive heart failure (CHF). Secondary end points included the evaluation of the 6-week rate of severe CHF as well as the 1-year mortality rate. After 6 weeks of treatment, zofenopril significantly reduced both the incidence of the primary end point (risk reduction 65%, 95% CI 20-80, 2P = .003) and the 6-week incidence of severe CHF (84%, 95% CI 33-97, 2P = .006) in NSTEMI patients. One-year mortality was also significantly reduced by zofenopril treatment (43%, 95% CI 14-57, 2P = .036). Results of this post hoc analysis of the SMILE Study strongly suggest the benefit of the early administration of zofenopril even in patients with an anterior wall NSTEMI.

Heart of Darkness: The Downside of Trastuzumab

Heart of Darkness: The Downside of Trastuzumab

Gender-specific risk factors for mortality associated with incident coronary heart disease—A prospective community-based study

Background. Risk factors for mortality in community-residing persons developing congestive heart failure (CHF) and acute myocardial infarction (AMI) may differ for males and females. Method. Persons from the Groningen Longitudinal Aging Study with incident CHF ( N = 274) or AMI ( N = 198) were identified between 1993 and 1998 and their survival status was collected in 2001. Risk factors are assessed prior to the cardiac diagnosis. Results. The 1-, 5-, 7-year survival rates were 65, 53, 50% for AMI and 74, 45, 32% for CHF. Multivariate analyses showed that male gender, high age, smoking, diabetes and low physical function were risk factors for mortality among persons with CHF. For AMI, 1 month mortality was related to high age and baseline low body mass index, while longer term mortality was related to male gender and high age. In addition, diabetes increased longer term mortality among females but not among males with AMI. Depression was not a risk factor for mortality for either condition in either gender. Conclusion. Males with CHF or AMI have worse survival rates compared to females. Risk factors for mortality are predominantly similar for males and females, except for diabetes which is a risk factor among females, but not males with AMI.

Heart Failure at the End of Life: Symptoms, Function, and Medical Care in the Cardiovascular Health Study

Among Cardiovascular Health Study participants who died from coronary heart disease, the authors compared those with incident and definite congestive heart failure (CHF) (n=60; 15%) and those with prevalent or probable CHF (n=70; 17.5%) to those with no history of CHF (n=198; 50%) concerning health status at the end of life. Both CHF groups had worse health status before death than the group without CHF. Patients in the CHF groups were more likely to use benzodiazepines (20% and 19% vs. 6%; p=0.001) and to rate their health as fair or poor (68% and 63% vs. 41%; p<0.001). They were more likely to be hospitalized (33% and 28% vs. 11%; p<0.001), to have activity restrictions (79% and 62% vs. 38%; p<0.001), and to report a wide array of physical symptoms. These data suggest that patients who die from coronary heart disease in the presence of CHF have greater need for hospice or palliative care than those with no history of CHF.

The Association of Alcohol Consumption and Incident Heart Failure: The Cardiovascular Health Study

We investigated the association between alcohol consumption and incident congestive heart failure (CHF) both overall and after adjusting for incident myocardial infarction (MI). Moderate alcohol consumption has been associated with lower risk of CHF and MI. The Cardiovascular Health study, a prospective cohort study of cardiovascular disease risk factors and outcomes, followed 5,888 subjects > or =65 years old for 7 to 10 years. Cox models were used to estimate the adjusted risk of CHF by reported alcohol consumption. There were 5,595 subjects at baseline at risk for incident CHF with alcohol data and 1,056 events during follow-up. Compared with abstainers, the adjusted risk of CHF was lower among subjects who reported consuming 1 to 6 drinks per week (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.67 to 1.00, p = 0.05) and 7 to 13 drinks per week (HR 0.66, 95% CI 0.47 to 0.91, p = 0.01). Time-dependent adjustment for incident MI altered only slightly the association between moderate alcohol consumption and CHF (for 1 to 6 drinks per week, HR 0.84, 95% CI 0.65 to 1.04; for 7 to 13 drinks per week, HR 0.69, 95% CI 0.49 to 0.99). Baseline former drinkers had a higher risk of CHF than abstainers (HR 1.51, p < 0.01), but those who quit during the study did not have a higher risk (HR 0.83, 95% CI 0.66 to 1.03). Moderate alcohol use is associated with a lower risk of incident CHF among older adults, even after accounting for incident MI and other factors.

Letter by Lehmann Regarding Articles “Electrocardiographic Abnormalities That Predict Coronary Heart Disease Events and Mortality in Postmenopausal Women: The Women’s Health Initiative” and “Electrocardiographic Predictors of Incident Congestive Heart Failure and All-Cause Mortality in Postmenopausal Women: the Women’s Health Initiative”

HomeCirculationVol. 113, No. 23Letter by Lehmann Regarding Articles “Electrocardiographic Abnormalities That Predict Coronary Heart Disease Events and Mortality in Postmenopausal Women: The Women’s Health Initiative” and “Electrocardiographic Predictors of Incident Congestive Heart Failure and All-Cause Mortality in Postmenopausal Women: the Women’s Health Initiative” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Lehmann Regarding Articles “Electrocardiographic Abnormalities That Predict Coronary Heart Disease Events and Mortality in Postmenopausal Women: The Women’s Health Initiative” and “Electrocardiographic Predictors of Incident Congestive Heart Failure and All-Cause Mortality in Postmenopausal Women: the Women’s Health Initiative” Michael H. Lehmann Michael H. LehmannMichael H. Lehmann Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Mich Search for more papers by this author Originally published13 Jun 2006https://doi.org/10.1161/CIRCULATIONAHA.106.622530Circulation. 2006;113:e854To the Editor:I read with interest the extensive analyses recently published by Rautaharju et al1 identifying traditional and nontraditional ECG predictors of coronary heart disease (CHD) events and mortality and incident congestive heart failure and all-cause mortality2 in a population of more than 38 000 postmenopausal women (Women’s Health Initiative participants). QT interval was the studied ECG index of repolarization duration, with rate adjustment achieved by using a linear function of the RR interval (QTrr). The authors reported that in their multiadjusted multiple ECG variable models, a prolonged QTrr (≥437 ms) was predictive of combined fatal and nonfatal CHD events among study subjects with preexisting cardiovascular disease (CVD) but not in those free of CVD and was predictive of CHD-related mortality in the CVD-free group. Furthermore, prolonged QTrr was predictive of incident congestive heart failure (regardless of preexisting CVD status) and all-cause mortality (CVD group only). The lower 95% confidence limits for the corresponding statistically significant hazard ratios ranged from 1.02 to 1.25.Although patients with major ventricular conduction defects (QRS duration ≥120 ms) were excluded from the study, the authors did not include QRS duration among the covariates in their statistical models. This is a potentially important methodologic omission, considering that QRS duration constitutes the initial portion of the QT interval. Indeed, Dr Rautaharju previously reported3 that QRS duration had a modest but highly significant (P<0.001) influence on the QT interval in a regres-sion model that included a rate correction factor. Moreover, from a pathophysiological standpoint, QRS duration (even if <120 ms) is likely to be relatively more prolonged in individuals with varying degrees of myocardial fibrosis and/or left ventricular hypertrophy, a well known epidemiological risk factor for adverse cardiac prognosis. However, as recently reviewed,4 none of the widely cited prior studies investigating rate-corrected QT interval as an ECG predictor of cardiovascular mortality in broad populations has addressed the potential confounding effect of QRS duration. The Women’s Health Initiative database affords Rautaharju et al an excellent opportunity to fill in this persistent methodological gap in the literature, at least as it pertains to women.DisclosuresNone.1 Rautahajru PM, Kooperberg C, Larson JC, LaCroix A. Electrocardiographic abnormalities that predict coronary heart disease events and mortality in postmenopausal women: the Women’s Health Initiative. Circulation. 2006; 113: 473–480.LinkGoogle Scholar2 Rautaharju PM, Kooperberg C, Larson JC, LaCroix A. Electrocardiographic predictors of incident congestive heart failure and all-cause mortality in postmenopausal women: the Women’s Health Initiative. Circulation. 2006; 113: 481–489.LinkGoogle Scholar3 Zhou SH, Wong S, Rautaharju PM, Karnik N, Calhoun HP. Should the JT rather than the QT interval be used to detect prolongation of ventricular repolarization? An assessment in normal conduction and in ventricular conduction defects. J Electrocardiol. 1992; 25 (suppl): 131–136.CrossrefMedlineGoogle Scholar4 Lehmann MH, Morady F. QT interval: metric for cardiac prognosis? Am J Med. 2003; 115: 732–734.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails June 13, 2006Vol 113, Issue 23 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.106.622530PMID: 16769921 Originally publishedJune 13, 2006 PDF download Advertisement SubjectsArrhythmiasChronic Ischemic Heart DiseaseCongenital Heart DiseaseCoronary CirculationElectrocardiology (ECG)Epidemiology

Response to Letter Regarding Articles “Electrocardiographic Abnormalities That Predict Coronary Heart Disease Events and Mortality in Postmenopausal Women: The Women’s Health Initiative” and “Electrocardiographic Predictors of Incident Congestive Heart Failure and All-Cause Mortality in Postmenopausal Women: the Women’s Health Initiative”

We appreciate Dr Lehmann’s supportive comments on our articles1,2 in Circulation . Dr Lehmann also brings up a relevant question: Why did we not include QRS duration as a covariate in our QT adjustment models? This question was examined in some detail in previous publications.3,4 Adding the QRS interval as …

Vitamin E increases the risk of developing heart failure after myocardial infarction: results from the GISSI-Prevenzione trial

Although results from basic science suggested a protective role of vitamin E treatment in the prevention of cardiovascular disease, recent evidence indicates increased cardiovascular mortality due to vitamin E treatment. Recently, the HOPE trial showed an increment of the incidence of congestive heart failure (CHF) in patients treated with vitamin E. We explored the effect of vitamin E on development of CHF in 8415 postinfarction patients without CHF at baseline, with an echocardiographic measure of left ventricular ejection fraction, who have been followed up for 3.5 years in the GISSI-Prevenzione trial. CHF during follow-up was defined as hospitalization or death for CHF. Cox regression models adjusted for relevant prognostic indicators were fitted. Main clinical characteristics were balanced in the 4202 and 4213 patients allocated vitamin E and control group, respectively. During follow-up, 220 patients (2.6%) developed CHF. Patients allocated vitamin E had a nonsignificant 20% (95% confidence intervals 0.92-1.56, P = 0.18) increased risk of developing CHF. Vitamin E treatment, however, was associated with a significant 50% increase (95% confidence intervals 1.03-2.20, P = 0.034) of CHF in patients with left ventricular dysfunction (ejection fraction < 50%). Our results confirm and extend previous evidence on the possible harmful effect of vitamin E on ventricular function in patients with cardiovascular disease. Available evidence should discourage the use of vitamin E in patients with left ventricular dysfunction.

Minimally Invasive Reoperative Isolated Valve Surgery: Early and Mid-Term Results

Minimally invasive, nonsternotomy approaches for valve procedures may reduce the risks associated with cardiac surgery after prior sternotomy and may improve outcomes. We analyzed our institutional experience to test this hypothesis. Between 1995 and 2002, 498 patients with previous cardiac operations via sternotomy underwent isolated valve surgery: 337 via median sternotomy (aortic = 160; mitral = 177) and 161 via mini-thoracotomy (aortic = 61; mitral = 100). Data were collected prospectively using the New York State Cardiac Surgery Report Form. Preoperative incidences of congestive heart failure, renal disease, and nonelective procedures were higher in the sternotomy group. Hospital mortality was significantly lower with the minimally invasive approach, 5.6% (9/161) versus 11.3% (38/337) (univariate, p = 0.04). However, multivariate analysis (odds ratio: 95% confidence intervals, p value) revealed that chronic obstructive pulmonary disease (6.6: 1.4 to 3.1, p = 0.001), renal disease (4.1: 1.52 to 11.2, p = 0.01), cerebrovascular disease (2.2: 1.03 to 4.78, p = 0.04), and ejection faction <30% (1.5: 0.96 to 5.5, p = 0.06) were associated with increased mortality. While mean bypass time, cross-clamp times, and stroke rates were comparable between groups, patients undergoing minimally invasive valve surgery had no deep wound infections (0% vs 2.4%, p = 0.05), less need for blood products (p = 0.02), and shorter hospital stays (p = 0.009). Five-year survival was higher with minimally invasive techniques as compared to a sternotomy approach (92.4 +/- 2% and 86.0 +/- 2%, respectively, p = 0.08). Reoperative valve surgery can be safely performed using a nonsternotomy, minimally invasive approach, with at least equal mortality, less hospital morbidity, decreased hospital length of stay, and slightly favorable mid-term survival as compared to sternotomy.

Impact of Congestive Heart Failure in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes

The presence of congestive heart failure (CHF) has been associated with treatment disparities and worse outcomes in patients with ST-segment elevation myocardial infarction, but the incidence and effect of CHF in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACSs) has not been well characterized. We evaluated 45,744 patients with NSTE ACS (positive cardiac markers and/or ischemic ST-segment changes) who were treated at 424 hospitals in the CRUSADE Quality Improvement Initiative between March 2000 and March 2003. Treatment patterns and in-hospital outcomes in patients with signs of CHF on presentation and those who developed in-hospital CHF were compared with those in patients without CHF. In total, 10,398 patients (22.7%) had signs of CHF on presentation, and 1,664 patients (3.6%) later developed in-hospital CHF. Compared with patients without CHF, early (<24 hours from presentation) medications and invasive cardiac procedures were used less often in patients with signs of CHF on presentation. Likewise, patients with in-hospital CHF were less likely than those without CHF to receive acute antiplatelet agents and undergo cardiac catheterization but more likely to receive acute beta blockers, angiotensin-converting enzyme inhibitors, and heparin and to undergo coronary artery bypass grafting. Adjusted mortality was higher in patients with signs of CHF on presentation (odds ratio 2.64, 95% confidence interval 2.31 to 3.01) and those with in-hospital CHF (odds ratio 4.93, 95% confidence interval 4.05 to 5.99) than in patients without CHF. In conclusion, CHF occurs frequently in patients with NSTE ACS but is associated with less aggressive treatment and a higher risk of mortality. Further study is needed to determine the causes of these treatment differences and the optimal therapeutic approach for patients with NSTE ACS and concomitant CHF.

Electrocardiographic QRS Duration and the Risk of Congestive Heart Failure

Prolonged electrocardiographic QRS duration is frequently observed in congestive heart failure (CHF) patients. We hypothesized that CHF risk increases with longer QRS interval in individuals free of CHF. We evaluated 1759 Framingham Study participants (mean age, 69 years; 63% women) without prior myocardial infarction or CHF who attended a routine examination. QRS duration was analyzed as a continuous (log-transformed) and a categorical variable [referent, <100 ms; incomplete bundle branch block (BBB), 100 to 119 ms; complete BBB, > or =120 ms]. During follow-up (mean, 12.7 years), 324 participants (205 women) developed CHF. CHF incidence increased across the 3 baseline QRS duration categories in both sexes. Each SD increment in log-QRS duration was associated with a multivariable-adjusted 23% increase in CHF risk [95% confidence interval [CI] 8% to 38%; P<0.001]. In time- dependent models with QRS category and risk factors updated every 2 years, incomplete BBB was associated with a 1.4-fold (95% CI, 1.05 to 1.96; P=0.03) and complete BBB with a 1.7-fold (95% CI, 1.28 to 2.35; P<0.001) risk of CHF. These associations were maintained on adjustment for baseline left ventricular mass. In our community-based sample, longer electrocardiographic QRS was associated with increased CHF risk, consistent with the hypothesis that depolarization delay may increase CHF risk.

Translocation of Ultrafine Particles

We read with great interest the article by Geiser et al. (2005) on the mechanism of translocation of ultrafine particles (UFPs) across cellular membranes in vivo in rats following inhalation and in vitro using porcine pulmonary macrophages and human red blood cells.

Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane®) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy

Background: Anthracycline-induced cardiotoxicity has led to the adoption of empirical dose limits that may restrict continued use of anthracyclines among patients who might benefit. Dexrazoxane, a cardioprotective agent, has been shown to reduce the risk of anthracycline-associated cardiotoxicity when given from first dose of anthracycline. This study sought to confirm the benefit of dexrazoxane in patients at high risk of cardiotoxicity due to prior anthracycline use.Patients and methods: A total of 164 female breast cancer patients, previously treated with anthracyclines, received anthracycline-based chemotherapy either with (n = 85) or without (n = 79) dexrazoxane for a maximum of six cycles.Results: Compared with those receiving anthracycline alone, patients treated with dexrazoxane experienced significantly fewer cardiac events (39% versus 13%, P < 0.001) and a lower and less severe incidence of congestive heart failure (11% versus 1%, P < 0.05). Tumor response rate was unaffected by dexrazoxane therapy. The frequency of adverse events was similar between groups and there were no significant between-group differences in the number of dose modifications/interruptions.Conclusion: Dexrazoxane significantly reduced the occurrence and severity of anthracycline-induced cardiotoxicity in patients at increased risk of cardiac dysfunction due to previous anthracycline treatment without compromising the antitumor efficacy of the chemotherapeutic regimen.