Circ Res. 2009 May 28; Hikoso S, Yamaguchi O, Nakano Y, Takeda T, Omiya S, Mizote I, Taneike M, Oka T, Tamai T, Oyabu J, Uno Y, Matsumura Y, Nishida K, Suzuki K, Kogo M, Hori M, Otsu KCardiomyocyte death plays an important role in the pathogenesis of heart failure. The nuclear factor (NF)-kappaB signaling pathway regulates cell death, however, the effect of NF-kappaB pathway on cell death can vary in different cells or stimuli. The purpose of the present study was to clarify the in vivo role of the NF-kappaB pathway in response to pressure overload. First, we subjected C57Bl6/J mice to pressure overload by means of transverse aortic constriction (TAC) and examined the activity of the NF-kappaB pathway in response to pressure overload. IkappaB kinase (IKK) and NF-kappaB were activated after TAC. Then, we investigated the role of the activation using cardiac-specific IKKbeta-deficient mice (CKO). CKO displayed normal global cardiac structure and function compared with control littermates. We subjected CKO and control mice to pressure overload. One week after TAC, CKO showed cardiac dilation, dysfunction, and lung congestion, which are characteristics of heart failure. The number of apoptotic cells in the hearts of CKO mice increased significantly after TAC. The levels of manganese superoxide dismutase mRNA and protein expression in CKO after TAC were significantly attenuated compared with control mice. The levels of oxidative stress and c-Jun N-terminal kinase (JNK) activation in CKO after TAC were significantly greater than those in control mice. Isoproterenol-induced cell death of isolated adult CKO cardiomyocytes was inhibited by treatment with either a manganese superoxide dismutase mimetic or a JNK inhibitor. Thus, the IKKbeta/NF-kappaB signaling pathway plays a protective role in cardiomyocytes because of the attenuation of oxidative stress and JNK activation in a setting of acute pressure overload.

J Card Fail. 2009 Jun; 15(5): 385-393Udelson JE, Pressler SJ, Sackner-Bernstein J, Massaro J, Ordronneau P, Lukas MA, Hauptman PJ, BACKGROUND: Suboptimal compliance in taking guideline-based pharmacotherapy in patients with chronic heart failure (HF) potentially increases the burden of hospitalizations and diminishes quality of life. By simplifying the medical regimen, once-daily dosing can potentially improve compliance. The Compliance And Quality of Life Study Comparing Once-Daily Controlled-Release Carvedilol CR and Twice-Daily Immediate-Release Carvedilol IR in Patients with Heart Failure (CASPER) Trial was designed to measure differential compliance, satisfaction, and quality of life in chronic HF patients taking carvedilol immediate release (IR) twice daily versus the bioequivalent carvedilol controlled-release (CR) once daily. METHODS AND RESULTS: CASPER was a prospective multicenter, 3-arm, parallel-group, randomized clinical trial for a 5-month period. The primary objective of the study was to evaluate and compare compliance with carvedilol IR twice daily (BID) and carvedilol phosphate CR once daily (QD) in patients with chronic HF who were taking carvedilol IR. Secondary objectives included comparisons of quality of life (Kansas City Cardiomyopathy Questionnaire), satisfaction with medication, and brain natriuretic peptide levels between subjects taking the two formulations. A total of 405 patients with chronic HF and left ventricular dysfunction were randomized to: (A) carvedilol IR twice daily, given double blind; (B) carvedilol CR taken in the morning and placebo in the afternoon, given double blind; or (C) carvedilol CR once daily, open label. Compliance was measured using the medication event monitoring system that captures time of bottle opening. The primary end point was a comparison of taking compliance (doses taken divided by total number of prescribed doses over the actual duration of the study) between the double-blind carvedilol IR BID versus the open-label carvedilol CR QD groups. Sample size estimates were based on assumptions of 75% compliance with BID dosing and 90% compliance with QD dosing. Mean compliance with carvedilol IR BID was 89.3% compared with 88.2% for carvedilol CR QD, and differential mean compliance was 1.1% (95% CI -4.4%, 6.6%; ie, not significant). There were no statistically significant differences in compliance between any of the 3 groups, nor differences in quality of life, treatment satisfaction, or physiologic measures among the 3 study arms. There were also no significant differences in adverse events or side effects among patients switching from carvedilol IR to carvedilol CR in arms B or C over the 5-month study duration compared with patients remaining on carvedilol IR. CONCLUSIONS: Compliance among chronic HF patients in the CASPER trial was high at baseline and unaffected by QD versus BID dosing. Over the 5-month follow-up period, there were no differences in adverse events among patients switching from carvedilol IR to CR.

J Cancer Surviv. 2009 May 28; Kinahan KE, Gandhi M, Lacouture ME, Eilers R, Haryani A, Didwania A, Sharp LKINTRODUCTION: Common late effects experienced by childhood cancer survivors include: thyroid disturbances, pulmonary compromise, heart failure, and secondary neoplasms. Dermatologic issues have been largely unexplored. METHODS: This descriptive study consisted of an 8 item self-reported questionnaire on dermatologic issues and the Dermatology Life Quality Index. Participants reported dermatological issues that presented anytime after their diagnosis of cancer. Over a seven month period, 166 survivors seen in a specialized program for adult survivors of childhood cancer housed within an adult cancer center received a cover letter either through the mail or in the clinic setting which explained the purpose of the study. A total of 78 survivors completed the study with an average age of 29.7 years (range 19-46) and an average time since their diagnosis of 19.2 years (range 6-46). RESULTS: Dermatological issues were reported by 59.0% of survivors and 50% saw a dermatologist at least once for these concerns. Nine survivors (11.5%) reported a skin cancer and ten (12.82%) were affected by alopecia. Additionally, 26 (33.3%) of survivors reported scars related to cancer therapy as a dermatological issue, and 99% of survivors reporting scars said they did not resolve with time. DISCUSSION/CONCLUSIONS: There are a range of dermatologic issues experienced by adult childhood cancer survivors. In our non-representative sample, 50% of the survivors sought specialized care from a dermatologist for their concern. Additional research is needed to more clearly understand the extent of dermatologic issues and their impact upon quality of life in childhood cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Childhood cancer survivors may frequently seek care from primary care providers. It is important for these providers to be aware of the risks associated with cancer treatments.

J Cardiovasc Med (Hagerstown). 2009 May 26; Aleksova A, Sabbadini G, Merlo M, Pinamonti B, Barbati G, Zecchin M, Bussani R, Silvestri F, Iorio AM, Stolfo D, Dal Ferro M, Dragos AM, Meringolo G, Pyxaras S, Lo Giudice F, Perkan A, di Lenarda A, Sinagra GBACKGROUND: Few data are available in the literature regarding the characteristics and prognosis of asymptomatic patients with idiopathic dilated cardiomyopathy (DCM). AIM: To determine the frequency with which patients affected by DCM are diagnosed in the asymptomatic state as well as to evaluate the natural history of such patients and the factors influencing their outcome. Moreover, we sought to compare the outcome of asymptomatic patients with that of patients with signs of overt heart failure at the time of first evaluation. METHODS AND RESULTS: We analyzed the data of 747 patients with DCM enlisted in the Heart Muscle Disease Registry of Trieste from 1978 to 2007. We divided our population into four groups; group 1 comprised 118 asymptomatic [New York Heart Association (NYHA) I] patients without a history of congestive symptoms (16%), group 2 comprised 102 asymptomatic (NYHA I) patients (14%) with a positive anamnesis for heart failure stabilized in medical therapy, group 3 comprised 327 patients (44%) with signs of mild heart failure (NYHA II) and group 4 comprised 200 patients (26%) in NYHA III-IV. During the follow-up of 112 +/- 63 months, 46 (21%) of 220 asymptomatic patients with DCM died or underwent heart transplantation. By Cox proportional model, left ventricular ejection fraction of 30% or less was a unique independent predictor either for death/heart transplantation (hazard ratio 3.15, 95% confidence interval 1.5-6.7, P = 0.003) or for sudden death/major ventricular arrhythmias (hazard ratio 3.9, 95% confidence interval 1.7-9.3, P = 0.002). Patients from group 1 had a trend for a better outcome with respect to those from group 2 (P = 0.06). In comparison with the asymptomatic patients, those with signs of overt heart failure at baseline had a worse prognosis. CONCLUSION: The proportion of asymptomatic patients with DCM at the moment of first evaluation at our center is significant (30%). Among them, those without a previous history of heart failure had a less advanced disease and a trend for a better long-term outcome on optimal medical treatment. Therefore, early diagnosis may offer better long-term quality of life and even better survival. Further studies on larger populations are indicated.

Value Health. 2009 May 15; Hays RD, Kim S, Spritzer KL, Kaplan RM, Tally S, Feeny D, Liu H, Fryback DGObjective: We evaluate the effects of mode and order of administration on health-related quality of life (HRQOL) scores. Method: We analyzed HRQOL data from the Clinical Outcomes and Measurement of Health Study (COMHS). In COMHS, we enrolled patients with heart failure or cataracts at three sites (University of California, San Diego, University of California, Los Angeles, and University of Wisconsin). Patients completed self-administered HRQOL instruments at baseline and months 1 and 6 post-baseline, including the EuroQol (EQ-5D), Health Utilities Index (HUI), Quality of Well-Being Scale-self-administered (QWB-SA), and the Short Form (SF)-36v2. At the 6 months follow-up, individuals were randomized to mail or telephone administration first, followed by the other mode of administration. We used repeated measures mixed effects models, adjusting for site, patient age, education, gender, and race. Results: Included were 121 individuals entering a heart failure program and 326 individuals scheduled for cataract surgery who completed the survey by mail or phone at the 6-month follow-up. The majority of the sample was female (53%) and white (86%). About a quarter of the sample had high school education or less (26%). The average age was 66 (36-91 range). HRQOL scores were higher (more positive) for phone administration following mail administration. The largest differences in scores between phone and mail responses occurred for comparisons of telephone responses for those who were randomized to a mail survey first compared with mail responses for those randomized to a telephone survey first (i.e., mode effects for responses that were given on the second administration of the HRQOL measures). The QWB-SA was the only measure that did not display the pattern of mode effects. The biggest differences between modes were 4 points on the SF-36v2 physical health and mental health component summary scores, 0.06 on the SF-6D, 0.03 on the QWB-SA, 0.08 on the EQ-5D, 0.04 on the HUI2, and 0.10 on the HUI3. Conclusions: Telephone administration yields significantly more positive HRQOL scores for all of the generic HRQOL measures except for the QWB-SA. The magnitude of effects was clearly important, with some differences as large as a half-standard deviation. These findings confirm the importance of considering mode of administration when interpreting HRQOL scores.

Cardiovasc Res. 2009 May 21; Tavares NI, Philip-Couderc P, Baertschi AJ, Lerch R, Montessuit CAIMS: Angiotensin II (Ang II) and tumor necrosis factor alpha (TNFalpha) are involved in the progression from compensated hypertrophy to heart failure. Here we test their role in the remodeling of ATP-dependent potassium channel (K(ATP)) in heart failure, conferring increased metabolic and diazoxide sensitivity. Methods and Results We observed increased expression of both angiotensinogen and TNFalpha in the failing rat myocardium, with a regional gradient matching that of the K(ATP) subunit Kir6.1 expression. Both angiotensinogen and TNFalpha expression correlated positively with Kir6.1 and negatively with Kir6.2 expression across the post-infarction myocardium. To further identify a causal relationship, cardiomyocytes isolated from normal rat hearts were exposed in vitro to Ang II or TNFalpha. We observed increased Kir6.1 and SUR subunit and reduced Kir6.2 subunit mRNA expression in cardiomyocytes cultured with Ang II or TNFalpha, similar to what was observed in failing hearts. In patch-clamp experiments, cardiomyocytes cultured with Ang II or TNFalpha exhibited responsiveness to diazoxide, in terms of both K(ATP) current and action potential shortening. This was not observed in untreated cardiomyocytes, and resembles the diazoxide sensitivity of failing cardiomyocytes that also overexpress Kir6.1. Ang II exerted its effect through induction of TNFalpha expression, because TNFalpha-neutralizing antibody abolished the effect of Ang II, and in failing hearts regional expression of angiotensinogen matched TNFalpha expression. Finally, Ang II and TNFalpha regulated K(ATP) subunit expression, possibly through differential expression of Forkhead box transcription factors. CONCLUSIONS: This study identifies Ang II and TNFalpha as mediators of the remodeling of K(ATP) channels in heart failure.

Heart. 2009 May 17; Jaber WA, Sorajja P, Borlaug BA, Nishimura RAObjective. To identify unique hemodynamic parameters that differentiate severe tricuspid regurgitation from constrictive pericarditis. Background. Severe tricuspid regurgitation, constrictive pericarditis and restrictive cardiomyopathy can all present with signs and symptoms of right heart failure and similar hemodynamic findings of elevation and equalization of diastolic pressures at catheterization. Although catheterisation findings of enhancement of ventricular interaction is a reliable parameter to distinguish constrictive pericarditis from restrictive cardiomyopathy, this also may be present in severe tricuspid regurgitation. Methods. Hemodynamic findings from simultaneous right and left heart catheterization of 14 patients (age 59 yrs; men 72%) with documented severe tricuspid regurgitation (Group I) were compared to those of 14 patients with surgically proven constrictive pericarditis (Group II). Results. Findings of elevated right atrial pressure, early rapid ventricular filling, and expiratory equalization of ventricular diastolic pressures were similar in both groups. Ventricular interdependence, assessed by interaction of left ventricular and right ventricular systolic pressures, was also present in both groups. Relative changes in LV and RV diastolic pressures during respiration reliably distinguished Group I from Group II. During inspiration, the difference between the LV and RV diastolic pressures widened in Group I but was narrowed in Group II. The height and slope of the early rapid filling wave in RV pressure trace was accentuated during inspiration in Group I but did not change in Group II. Conclusions. The hemodynamic findings at cardiac catheterization in patients with severe, symptomatic tricuspid regurgitation are similar to those of constrictive pericarditis. Careful analysis of the relationship of the LV and RV diastolic pressures during respiration can help differentiate the two entities.

Endocrinology. 2009 May 21; Klusonová P, Reháková L, Borchert G, Vagnerová K, Neckár J, Ergang P, Miksík I, Kolár F, Pácha JCorticosteroids are known to not only regulate electrolyte homeostasis but also to play a role in the cardiovascular system, including myocardial remodeling. Because transgenic mice that overexpress 11beta-hydroxysteroid dehydrogenase type 2 (11HSD2) in cardiomyocytes have been shown to spontaneously develop cardiac hypertrophy and fibrosis, we investigated whether changes in the cardiac metabolism of glucocorticoids accompany remodeling of the heart under physiological conditions. In the present study, glucocorticoid metabolism and 11HSD2 were explored in the hearts of rats exposed to chronic intermittent hypobaric hypoxia (CIH), which induces hypertrophy and fibrosis of the right and less of the left ventricle. We first demonstrated that adaptation to CIH led to a significant increase in 11HSD2 transcript levels and activity in the myocardium. In contrast, neither 11HSD1 activity and mRNA level nor the abundance of mineralocorticoid (MR) and glucocorticoid receptor (GR) mRNA were upregulated. The adaptation to CIH also led to an increase of 11HSD2 mRNA in isolated cardiomyocytes, whereas 11HSD1, GR and MR mRNA levels were not changed in comparison with the cardiomyocytes of control normoxic rats. The changes in cardiac metabolism of glucocorticoids were accompanied by inflammatory responses. The expression levels of the proinflammatory markers cyclooxygenase-2 and osteopontin were significantly increased in both the myocardium and the cardiomyocytes isolated from rats exposed to CIH. These findings suggest that myocardial remodeling induced by CIH is associated with the upregulation of cardiac 11HSD2. Consequently, local metabolism of glucocorticoids could indeed play a role in cardiac hypertrophy, fibrosis and subsequent progression to heart failure.

Circulation. 2009 May 26; Kvakan H, Kleinewietfeld M, Qadri F, Park JK, Fischer R, Schwarz I, Rahn HP, Plehm R, Wellner M, Elitok S, Gratze P, Dechend R, Luft FC, Muller DNBACKGROUND: -Hypertensive target organ damage, especially cardiac hypertrophy with heart failure and arrhythmia, is a major source of morbidity and mortality. Angiotensin II, a major mediator of hypertension and cardiac damage, has proinflammatory properties. Inflammation and activation of the immune system play a pivotal role in pathogenesis of hypertensive target organ damage. However, the role of immunosuppressive CD4(+)CD25(+) regulatory T (Treg) cells in the pathogenesis of hypertensive target organ damage is unexplored. Methods and Results-We conducted adoptive transfer of Treg cells into angiotensin II-infused hypertensive mice. Treg cell recipients exhibited improved cardiac hypertrophy and less cardiac fibrosis despite sustained hypertension. Amelioration of cardiac morphology was accompanied by an improvement in arrhythmogenic electric remodeling, indicating the functional significance of the enhanced cardiac morphology. Delocalization of the connexin 43 gap junction protein is one of the major pathomechanisms in electric remodeling. Pronounced connexin 43 immunoreactivity was found at the lateral borders of cardiomyocytes in angiotensin II-treated mice. In contrast, connexin 43 was restricted to the intercalated disk regions in sham controls. Surprisingly, angiotensin II+Treg-treated mice showed normal connexin 43 gap junction protein localization. Adoptive Treg cell transfer resulted in a marked reduction in cardiac CD4(+), CD8(+), and CD69(+) cell and macrophage infiltration. Conclusions-Immunosuppressive effects of transferred Treg cells ameliorated cardiac damage and accounted for the improved electric remodeling independently of blood pressure-lowering effects. Our results provide new insights into the pathogenesis of hypertensive cardiac damage and could therefore lead to new therapeutic approaches that involve manipulation of the immune system.

J Am Coll Cardiol. 2009 May 26; 53(21): 1975-80Giannoni A, Emdin M, Bramanti F, Iudice G, Francis DP, Barsotti A, Piepoli M, Passino COBJECTIVES: The aim of the present study was to investigate the prognostic significance of chemosensitivity to hypercapnia in chronic heart failure (HF). BACKGROUND: Increased chemosensitivity to hypoxia and hypercapnia has been observed in HF. The potential value of enhanced chemosensitivity to hypercapnia to risk prediction in systolic HF has not been specifically evaluated. METHODS: One hundred ten consecutive systolic HF patients (age 62 +/- 15 years, left ventricular ejection fraction [LVEF] 31 +/- 7%) underwent assessment of chemosensitivity to hypoxia and hypercapnia (rebreathing technique) and were followed up for a median period of 29 months (range 1 to 54 months). The end point was a composite of cardiac death and aborted cardiac death (ventricular tachyarrhythmia treated by cardioverter-defibrillator). RESULTS: At baseline, 31 patients (28%) had enhanced chemosensitivity to both hypoxia and hypercapnia. Although they had the same LVEF as the 43 patients (39%) with normal chemosensitivity, they were more symptomatic (New York Heart Association functional class), had higher plasma brain natriuretic peptide and norepinephrine, steeper regression slope relating minute ventilation to carbon dioxide output (V(E)/V(CO2) slope), more Cheyne-Stokes respiration, and more ventricular arrhythmias (all p < 0.05). Four-year survival was only 49%, in marked contrast to 100% for patients with normal chemosensitivity (p < 0.001). On multivariate analysis, combined elevation in chemosensitivity was the strongest independent prognostic marker, even when adjusted for univariate predictors (V(E)/V(CO2) slope, Cheyne-Stokes respiration, LVEF, and brain natriuretic peptide, p < 0.05). CONCLUSIONS: Increased chemosensitivity to both hypoxia and hypercapnia, eliciting neurohormonal derangement, ventilation instability, and ventricular arrhythmias, is a very serious adverse prognostic marker in HF.

Heart Rhythm. 2009 Jun; 6(6): 784-92Ogawa M, Morita N, Tang L, Karagueuzian HS, Weiss JN, Lin SF, Chen PSBACKGROUND: Successful defibrillation may be followed by recurrent spontaneous ventricular fibrillation (VF). The mechanisms of postshock spontaneous VF are unclear. OBJECTIVE: The purpose of this study was to determine the mechanisms of spontaneous VF after initial successful defibrillation in a rabbit model of heart failure (HF). METHODS: Simultaneous optical mapping of intracellular calcium (Ca(i)) and membrane potential (Vm) was performed in 12 rabbit hearts with chronic pacing-induced heart failure, in 4 sham-operated hearts, and in 5 normal hearts during fibrillation-defibrillation episodes. RESULTS: Twenty-eight spontaneous VF episodes were recorded after initial successful defibrillation in 4 failing hearts (SVF group) but not in the remaining 8 failing hearts (no-SVF group) or in the normal or sham-operated hearts. The action potential duration (APD(80)) before pacing-induced VF was 209 +/- 9 ms in the SVF group and 212 +/- 14 ms in the no-SVF group (P = NS). After successful defibrillation, APD(80) shortened to 147 +/- 26 ms in the SVF group and to 176 +/- 14 ms in the no-SVF group (P = .04). However, the duration of Ca(i) after defibrillation was not different between the two groups (246 +/- 21 ms vs 241 +/- 17 ms, P = NS), resulting in elevated Ca(i) during late phase 3 or phase 4 of the action potential. Standard glass microelectrode recording in an additional 5 failing hearts confirmed postshock APD shortening and afterdepolarizations. APD(80) of normal and sham-operated hearts was not shortened after defibrillation. CONCLUSION: HF promotes acute shortening of APD immediately after termination of VF in failing hearts. Persistent Ca(i) elevation during late phase 3 and phase 4 of the shortened action potential result in afterdepolarizations, triggered activity, and spontaneous VF.

J Cardiovasc Nurs. 2009 May 21; Granger BB, Sandelowski M, Tahshjain H, Swedberg K, Ekman IBACKGROUND AND RESEARCH OBJECTIVE:: Despite the known benefit of self-care strategies for symptom management in heart failure (HF), most patients are unable to perform self-care activities successfully. This study therefore examined how communication about the HF regimen between patients and their physicians is experienced and understood by both partners. SUBJECTS AND METHODS:: Six pairs (n = 12) of adult patients with HF who were admitted for acute symptom exacerbation and their physicians were interviewed for this qualitative descriptive study in the inpatient setting. Semistructured in-depth interviews were conducted. Data were analyzed using content analysis. RESULTS:: Both patients and providers described adherence to the HF regimen as "work." Both reported the same list of tasks and knowledge requirements as key components of the HF regimen, and both reported delegating their own regimen-related work to others. Despite these similarities, perceptions of the nature and complexity of the work of the HF regimen differed. Patients described the regimen as "hard work," but physicians perceived patients as nonparticipatory in self-care, in spite of the instructions being "easy." Patients perceived themselves as understanding what to do but needing help with how to carry out self-care. By contrast, physicians perceived patients as not understanding what the regimen requires and therefore needing more repetition of knowledge-based instructions. CONCLUSION:: The self-care regimen in chronic HF is characterized by both patients and physicians as work, but patient-physician dyads show divergent understandings of that work. Future research to improve adherence should move beyond the patient to look at the nature of the work itself and the relationship of the patient and caregivers to the work.

J Cardiovasc Med (Hagerstown). 2009 May 21; Loforte A, Montalto A, Ranocchi F, Casali G, Luzi G, Monica PL, Sbaraglia F, Polizzi V, Distefano G, Musumeci FOBJECTIVES: The excellent results with left ventricular assist devices (LVADs) have revolutionized the treatment options for end-stage heart failure. The use of pulsatile devices is associated with significant comorbidity and limited durability. The axial-flow HeartMate II LVAD represents the new generation of devices. The clinical use of this pump resulted in superior outcomes. We review the HeartMate II technology, management, clinical usage and our experience. METHODS: Between 3/2002 and 12/2008, 18 transplantable adult patients were supported on long-term HeartMate II LVAD at our institution (13 men, age 52 +/- 8.4 years, range: 31-64 years). Primary indications were: ischemic cardiomyopathy (CMP) (n = 13), idiopathic CMP (n = 5). All patients were in New York Heart Association (NYHA) Class IV heart failure. None of patients had prior open-heart surgery. Implantation via cannulation of the left ventricular apex and the ascending aorta was always elective. RESULTS: Mean support time was 217 +/- 212.3 days (range: 1-665 days). Early (30-day) mortality was 27.7% (five patients) with multiple organ failure and sepsis as main causes of death. Bleeding requiring reoperation occurred in six (33.3%) cases. Cerebral hemorrhage occurred in one patient. There were two driveline infections and no device failure. Twelve (66.6%) patients were successfully discharged home. Overall nine patients (50%) were transplanted and two patients are actually waiting for a suitable organ (n = 2 patients discharged home and n = 1 patient in hospital). At latest, follow-up survival rate after heart transplantation is 66.6% (six patients). CONCLUSION: Long-term HeartMate II LVAD provides good mid-term, long-term results. This new technology requires delicate management. Functional status and quality of life greatly improve in patients who survive the perioperative period.

Am J Physiol Heart Circ Physiol. 2009 May 22; Matsushima S, Kinugawa S, Yokota T, Inoue N, Ohta Y, Hamaguchi S, Tsutsui HType 2 diabetes adversely affects the outcomes in patients with myocardial infarction (MI), which is associated with the development of left ventricular (LV) failure. NAD(P)H oxidase-derived superoxide (O2(-)) production is increased in type 2 diabetes. However, its pathophysiological significance in advanced post-MI LV failure associated with type 2 diabetes remains unestablished. We thus hypothesized that an inhibitor of NAD(P)H oxidase activation, apocynin, could attenuate the exacerbated LV failure after MI in high-fat diet (HFD)-induced obese mice with type 2 diabetes. Male C57BL/6J mice were fed on either HFD or normal diet (ND) for 8 weeks. At 4 weeks of feeding, MI was created in mice by ligating left coronary artery. HFD-fed MI mice were treated with either apocynin or vehicle. HFD+MI had significantly greater LV end-diastolic diameter (LVEDD; 5.7+/-0.1 vs. 5.3+/-0.2mm), end-diastolic pressure (EDP; 12+/-2 vs. 8+/-1mmHg) and lung weight/tibial length (10.1+/-0.3 vs. 8.7+/-0.7mg/mm) than ND+MI, which was accompanied by an increased interstitial fibrosis of non-infarcted LV. Treatment of HFD+MI with apocynin significantly decreased LVEDD (5.4+/-0.1mm), LVEDP (9.7+/-0.8mmHg), lung weight/tibial length (9.0+/-0.3mg/mm), and concomitantly interstitial fibrosis of non-infarcted LV to ND+MI level without affecting body weight, glucose metabolism, and infarct size. NAD(P)H oxidase activity and O2(-) production were increased in non-infarcted LV tissues from HFD+MI, both of which were attenuated by apocynin to ND+MI level. Type 2 diabetes was associated with the exacerbation of LV failure after MI via increasing NAD(P)H oxidase-derived O2(-), which may be a novel important therapeutic target in advanced heart failure with diabetes. Key words: heart failure, diabetes, remodeling, antioxidants.

Toxicology. 2009 Jun 16; 260(1-3): 84-96Costa VM, Silva R, Tavares LC, Vitorino R, Amado F, Carvalho F, Bastos MD, Carvalho M, Carvalho RA, Remião FThe sustained elevation of plasma and interstitial catecholamine levels, namely adrenaline (ADR), and the generation of reactive oxygen species (ROS) are well recognized hallmarks of several cardiopathologic conditions, like cardiac ischemia/reperfusion (I/R) and heart failure (HF). The present work aimed to investigate the proteomics and energetic metabolism of cardiomyocytes incubated with ADR and/or ROS. To mimic pathologic conditions, freshly isolated calcium-tolerant cardiomyocytes from adult rat were incubated with ADR alone or in the presence of a system capable of generating ROS [(xanthine with xanthine oxidase) (XXO)]. Two-dimensional electrophoresis with matrix-assisted laser desorption/ionization and time-of-flight mass spectrometer analysis were used to define protein spot alterations in the cardiomyocytes incubated with ADR and/or ROS. Moreover, the energetic metabolism and the activity of mitochondrial complexes were evaluated by nuclear magnetic resonance and spectrophotometric determinations, respectively. The protein extract was mainly constituted by cardiac mitochondrial proteins and the alterations found were included in five functional classes: (i) structural proteins, notably myosin light chain-2; (ii) redox regulation proteins, in particular superoxide dismutase (SOD); (iii) energetic metabolism proteins, encompassing ATP synthase alpha chain and dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex; (iv) stress response proteins, like the heat shock proteins; and (v) regulatory proteins, like cytochrome c and voltage-dependent anion channel 1. The XXO system elicited alterations in cardiac contractile proteins, as they showed high levels of cleavage, and also altered energetic metabolism, through increased lactate and alanine levels. The cardiomyocytes incubation with ADR resulted in an accentuated increase in mitochondrial complexes activity and the decrease in alanine/lactate ratio, thus reflecting a high cytosolic NADH/NAD(+) ratio. Furthermore, an increase in manganese SOD expression and total SOD activity occurred in the ADR group, as the increase in the mitochondrial complexes presumably led to higher 'electron leakage'. The modifications in proteins, enzymes activity, and energetic metabolism were indicative that different pathways are activated by catecholamines and ROS. These alterations altogether determine the I/R and HF specific features and contribute for the initiation or aggravation of those cardiopathologic conditions.

Heart Vessels. 2009 May; 24(3): 187-192Nishiyama M, Park IS, Yoshikawa T, Hatai Y, Ando M, Takahashi Y, Mori K, Murakami YThere have been few reports describing the use of carvedilol in children or patients with congenital heart disease. Therefore, its optimal regimen, efficacy, and safety in these patients have not been adequately investigated. Subjects were 27 patients with two functioning ventricles, for whom carvedilol was initiated (from December 2001 to December 2005) to treat heart failure. All patients had failed to respond to conventional cardiac medication. They consisted of 12 males and 15 females, aged 23 days to 47 years (median age: 2 years). Heart failure due to ischemia (myocardial infarction, intraoperative ischemic event) or due to myocardial disease (cardiomyopathy, myocarditis), and heart failure with atrial or ventricular tachyarrhythmia represented 70% of all cases. Carvedilol was initiated at a dose of 0.02-0.05 mg/kg/day, which was increased by 0.05-0.1 mg/kg/day after 2 days, 0.1 mg/kg/day after 5 days, and 0.05-0.1 mg/kg/day every month thereafter with a target dose of 0.8 mg/kg/day. This study retrospectively assessed the efficacy and adverse reactions based on changes of symptoms, cardiothoracic ratio (CTR), left ventricular ejection fraction (LVEF), and human atrial natriuretic peptide (hANP)/b-type natriuretic peptide (BNP) blood levels. The mean follow-up period was 10.2 months (range: 1-46 months). Twenty-six (96.3%) patients showed improvement in symptoms and were discharged from the hospital. However, the remaining one patient failed to respond and died. Significant cardiovascular adverse reaction was seen in none of the patients. The mean CTR decreased from 61.8% +/- 5.3% before treatment to 57.6% +/- 7.4% after treatment (P < 0.05, n = 25), and the mean LVEF improved from 41.4% +/- 23.1% to 61.1% +/- 10.1% (P < 0.05, n = 10), respectively. Mean hANP and BNP levels showed a decrease from 239.1 pg/ml to 118.3 pg/ml and a significant decrease from 437.9 pg/ml to 120.5 pg/ml, respectively (P < 0.05, n = 10). Improvements in these data were also demonstrated when analyzed individually among the pediatric group (aged younger than 18) and the congenital heart disease group. Initiation of carvedilol at a lower dose with more gradual dose escalation, compared with previously reported regimens, might have efficacy with low incidence of adverse effects in pediatric patients and patients with congenital heart disease. Carvedilol may be effective in treating heart failure in children due to ischemia, myocardial disease, and complicated by tachyarrhythmia.

J Am Soc Echocardiogr. 2009 May; 22(5): 478-485.e3Fornwalt BK, Sprague WW, Carew JD, Merlino JD, Fyfe DA, León AR, Oshinski JNBACKGROUND: Doppler tissue imaging (DTI) - based dyssynchrony parameters failed to predict response to cardiac resynchronization therapy (CRT) in the multicenter Predictors of Response to Cardiac Resynchronization Therapy (PROSPECT) trial. Large variability during the interpretation of DTI data was one of several factors thought to contribute to this failure. In this study, the authors hypothesized that using larger regions of interest (ROIs) to generate velocity curves from Doppler tissue images would significantly reduce the variability of DTI dyssynchrony parameters. METHODS: The variability of 3 ROI sizes (6 x 6, 18 x 6, and 30 x 6 mm) was compared in 30 patients undergoing CRT. Variability due to manual ROI placement was determined for each ROI size by placing 3 ROIs in each myocardial segment, 6mm apart from one another. Thus, 3 velocity curves were generated for each segment and each ROI size. Four published dyssynchrony parameters were calculated from all permutations of the 3 ROI positions per segment. A mean modified coefficient of variation was calculated for each parameter and ROI size. RESULTS: The 6 x 6 mm ROI had a mean coefficient of variation of 27%. The 18 x 6 and 30 x 6 mm ROIs had significantly lower coefficients of variation (17% and 14%, respectively) than the 6 x 6 mm ROI (P < .01 for both). The 30 x 6 mm ROI also reduced the diagnostic inconsistency of dyssynchrony parameters by 44% (P = .024) compared with the 6 x 6 mm ROI. CONCLUSION: Using a 30 x 6 mm ROI instead of a 6 x 6 mm ROI to quantify tissue Doppler dyssynchrony reduces variability by 47% and diagnostic inconsistency by 44%. The authors recommend using a 30 x 6 mm ROI in future trials to minimize variability.

J Am Coll Cardiol. 2009 May 26; 53(21): 1993-2005Kobayashi S, Yano M, Suetomi T, Ono M, Tateishi H, Mochizuki M, Xu X, Uchinoumi H, Okuda S, Yamamoto T, Koseki N, Kyushiki H, Ikemoto N, Matsuzaki MOBJECTIVES: We sought to investigate the effect of dantrolene, a drug generally used to treat malignant hyperthermia, on the Ca2+ release and cardiomyocyte function in failing hearts. BACKGROUND: The N-terminal (N: 1-600) and central (C: 2000-2500) domains of the ryanodine receptor (RyR) harbor many mutations associated with malignant hyperthermia in skeletal muscle RyR (RyR1) and polymorphic ventricular tachycardia in cardiac RyR (RyR2). There is strong evidence that interdomain interaction between these regions plays an important role in the mechanism of channel regulation. METHODS: Sarcoplasmic reticulum vesicles and cardiomyocytes were isolated from the left ventricular muscles of dogs (normal or rapid ventricular pacing for 4 weeks), for Ca2+ leak, transient, and spark assays. To assess the zipped or unzipped state of the interacting domains, the RyR was labeled fluorescently with methylcoumarin acetate in a site-directed manner. We used a quartz-crystal microbalance technique to identify the dantrolene binding site within the RyR2. RESULTS: Dantrolene specifically bound to domain 601-620 in RyR2. In the sarcoplasmic reticulum isolated from pacing-induced failing dog hearts, the defective interdomain interaction (domain unzipping) had already occurred, causing spontaneous Ca2+ leak. Dantrolene suppressed both domain unzipping and the Ca2+ leak, demonstrating identical drug concentration-dependence (IC50 = 0.3 micromol/l). In failing cardiomyocytes, both diastolic Ca2+ sparks and delayed afterdepolarization were observed frequently, but 1 micromol/l dantrolene inhibited both events. CONCLUSIONS: Dantrolene corrects defective interdomain interactions within RyR2 in failing hearts, inhibits spontaneous Ca2+ leak, and in turn improves cardiomyocyte function in failing hearts. Thus, dantrolene may have a potential to treat heart failure, specifically targeting the RyR2.

Transplant Proc. 2009 May; 41(4): 1357-9Loforte A, Montalto A, Ranocchi F, Casali G, Luzi G, Della Monica PL, Sbaraglia F, Polizzi V, Distefano G, Musumeci FBACKGROUND: The use of left ventricular assist devices (LVAD) is an accepted therapy for patients with refractory heart failure. The HeartMate II is a small (350 g), implantable, axial-flow pump (nonpulsatile flow), which is designed to support the left ventricle for extended periods of time. Here we have reported our initial single-center clinical experience with this device as a bridge to heart transplantation. MATERIALS AND METHODS: Between March 2002 and December 2008, 18 transplantable adult patients were supported on long-term HeartMate II LVAS at our institution. The cohort included 15 men with an overall mean age of 52 +/- 8.4 years (range, 31-64 years). Primary indications for implantation were ischemic cardiomyopathy (CMP; n = 13) and idiopathic CMP (n = 5). All heart failure patients were New York Heart Association (NYHA) functional class IV. None of them had undergone prior open heart surgery. Implantation was performed via cannulation of the left ventricular apex and ascending aorta, and in each case was an elective procedure. RESULTS: Mean support time was 217 +/- 212.3 days (range, 1-665 days). Early (30-day) mortality was 27.7% (n = 5) due to multiple organ failure and sepsis as main causes of death. Bleeding requiring reoperation occurred in 6 cases (33.3%). Cerebral hemorrhage occurred in 1 case. There were 2 driveline infections and no device failure. Twelve subjects (66.6%) were successfully discharged home. Overall, 9 patients (50%) underwent transplantation and 3 are awaiting a suitable organ (2 were discharged home and 1 is in hospital). At latest follow-up, the survival rate after heart transplantation was 66.6% (n = 6). CONCLUSIONS: Long-term HeartMate II LVAS can successfully bridge patients to heart transplantation. Good mid- and long-term results may support the use of this device even for a permanent solution in nontransplantable subjects.

J Surg Res. 2009 Jan 20; Matsumoto S, Iwata H, Shirahashi K, Saio M, Umeda Y, Marui T, Ishida N, Kimura M, Sugimoto T, Manabe H, Takemura HBACKGROUND: The objective of the present study was to investigate the effects of granulocyte colony-stimulating factor (G-CSF) on right ventricular hypertrophy following extensive pulmonary resection in rats. MATERIALS AND METHODS: Adult rats were divided into four groups: (1) Group S (right thoracotomy only); (2) Group L (right three lobectomy); (3) Group LG10 (Group L+G-CSF [10mug/kg/d]); and (4) Group LG100 (Group L+G-CSF [100mug/kg/d]). At postoperative day 21, weight ratio of the right ventricular to the left ventricle plus septum (RV/LV+S, indicator of right ventricular hypertrophy) were measured, and a histopathological study was conducted to determine percentage wall thickness of peripheral pulmonary arteries and proliferating cell nuclear antigen labeling index (indicator of oxidative DNA damage) of right ventricles. RESULTS: Mean RV/LV+S for Group S was 0.27+/-0.02, significantly smaller than that for the lobectomy groups (Group L, LG10, LG100; 0.47+/-0.05, 0.35+/-0.02, 0.38+/-0.05). G-CSF significantly suppressed right ventricular hypertrophy. Mean medial wall thickness of peripheral pulmonary arteries for Group S was 13.6% +/- 4.9%, significantly smaller than that for Group L (22.9% +/- 9.6%). Compared with Group L, G-CSF reduced medial wall thickness (LG10, 17.6% +/- 9.5%; LG100, 18.0% +/- 11.2%). Incidence of proliferating cell nuclear antigen positive nuclei for Group S was 1.07% +/- 0.49%, significantly smaller than that for Group L (13.77% +/- 5.87%). G-CSF significantly reduced the incidence of proliferating cell nuclear antigen positive nuclei (LG10, 4.04% +/- 2.14%; LG100, 3.18% +/- 1.66%). CONCLUSIONS: G-CSF administration not only reduce medial wall thickness of peripheral pulmonary arteries but also directly protect cardiomyocytes of the right ventricle, thus suppressing right ventricular hypertrophy. These results suggest that low-dose G-CSF administration can prevent right heart failure following extensive pulmonary resection.

Ann Intern Med. 2009 May 18; Mann JF, Schmieder RE, Dyal L, McQueen MJ, Schumacher H, Pogue J, Wang X, Probstfield JL, Avezum A, Cardona-Munoz E, Dagenais GR, Diaz R, Fodor G, Maillon JM, Rydén L, Yu CM, Teo KK, Yusuf S, BACKGROUND: Angiotensin-receptor blockers (ARBs) blunt progression of advanced diabetic nephropathy, but their long-term renal effects in other patients are not clear. OBJECTIVE: To examine the long-term renal effects of telmisartan versus placebo in adults at high vascular risk. DESIGN: Randomized trial. Patients were randomly assigned (by a central automated system) between November 2001 and May 2004 and were followed until March 2008. Participants and investigators were blinded to intervention status. SETTING: Multicenter, multinational study. PATIENTS: 5927 adults with known cardiovascular disease or diabetes with end-organ damage but without macroalbuminuria or heart failure who cannot tolerate angiotensin-converting enzyme inhibitors. INTERVENTION: Telmisartan, 80 mg/d (n = 2954), or matching placebo (n = 2972) plus standard treatment for a mean of 56 months. MEASUREMENTS: Composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated glomerular filtration rate (GFR), and changes in albuminuria. RESULTS: No important difference was found in the composite renal outcome with telmisartan (58 patients [1.96%]) versus placebo (46 patients [1.55%]) (hazard ratio, 1.29 [95% CI, 0.87 to 1.89]; P = 0.20). Among the telmisartan and placebo groups, 7 and 10 patients had dialysis and 56 and 36 patients had doubling of serum creatinine, respectively (hazard ratio, 1.59 [CI, 1.04 to 2.41]; P = 0.031). Albuminuria increased less with telmisartan than with placebo (32% [CI, 23% to 41%] vs. 63% [CI, 52% to 76%]; P < 0.001). Declines in estimated GFR were greater with telmisartan than with placebo (mean change in estimated GFR, -3.2 mL/min per 1.73 m(2) (SD, 18.3) vs. -0.26 mL/min per 1.73 m(2) (SD, 18.0); P < 0.001). Limitation: Few participants (n = 17) had dialysis. CONCLUSION: In adults with vascular disease but without macroalbuminuria, telmisartan's effects on major renal outcomes were similar to those of placebo. Primary Funding Source: Boehringer Ingelheim.

Cardiovasc Res. 2009 May 20; Kang YM, He RL, Yang LM, Qin DN, Guggilam A, Elks C, Yan N, Guo Z, Francis JAIMS: Increased proinflammatory cytokines after myocardial infarction augment the progression of heart failure (HF) and are of prognostic significance. Recently, we demonstrated that increased proinflammatory cytokines in the brains of HF rats increased paraventricular nucleus superoxide and down-regulated neuronal nitric oxide synthase (nNOS), contributing to sympathoexcitation. In this study, we explored the possible roles of brain proinflammatory cytokines and their effects on modulating paraventricular nucleus neurotransmitters in the exaggerated sympathetic activity in HF. METHODS: Sprague-Dawley rats with HF or sham-operated control (SHAM) rats were treated for 4 weeks with a continuous intracerebroventricular (ICV) infusion of the cytokine blockers, pentoxifylline (PTX, 10 microg/h and 40 microg/h) or etanercept (ETN, 5microg/h and 10 microg/h), or vehicle. Another set of HF and SHAM rats were treated with intraperitoneal (IP) infusion of a similar dose of PTX or ETN. RESULTS: HF rats had increased neuronal excitation accompanied by higher levels of glutamate, norepinephrine (NE) and tyrosine hydroxylase (TH), and lower levels of gamma-aminobutyric acid (GABA), nNOS and 67-kDa isoform of glutamate decarboxylase (GAD67) compared to SHAM rats. Plasma cytokines, NE, epinephrine, angiotensin II, and renal sympathetic nerve activity were also increased in HF rats. ICV treatment with low doses of PTX or ETN attenuated, and high doses prevented, the increased glutamate, NE and TH and decreased GABA, nNOS and GAD67 in the PVN and renal sympathetic nerve activity of HF rats. IP treatment with similar doses of PTX or ETN did not affect glutamate, NE, TH, GABA, nNOS and GAD67 in the paraventricular nucleus and had no effect on renal sympathetic nerve activity of HF rats. CONCLUSION: This study, for the first time, demonstrates that proinflammatory cytokines modulate neurotransmitters in the paraventricular nucleus and contribute to sympathoexcitation in HF.

Med Clin (Barc). 2009 May; 132S1: 48-54Fernández de Bobadilla J, López-Sendón JHeart failure (HF) is more prevalent and evolves more rapidly in patients with renal failure (RF). Renal failure not only produces myocardial damage, but also induces the development of clinical heart failure thus making the treatment of these patients more difficult. The incidence of HF in patients with RF is around 15%. Renal function in patients with RF is lower than in the general population. This is true for patients with preserved and depressed left ventricular ejection fraction (LVEF). HF mortality increases 30% for every 1-mg/dL increase in creatinine and renal function should always be considered when assessing the cardiovascular risk and therapeutic alternatives of cardiovascular patients. Angiotensin converting enzyme inhibitors, Angiotensin receptor blockers and aldosterone blockers may cause acute renal failure and serum creatinine and potassium should be closely monitored. Chronic RF is a human model of accelerated atherosclerosis. It induces a rapid progression of coronary atherosclerosis and make atherosclerotic plaques more vulnerable to acute coronary syndromes (ACS) because of coagulation changes inherent to RF. Ischemia is also more frequent due to the imbalance between oxygen requirements and supplies. Chronic RF is associated with a worse outcome in patients with ACS and increases the risk of bleeding, and is associated with a higher mortality in patients under surgical or percutaneous coronary revascularization. Of the patients treated with an interventional coronary procedure (ICP), 3,3% suffer acute RF. Saline administration at a dose of 1ml/kg/h for 12 hours before and 12 hours after ICP prevents the development of acute RF. Although the role of N-acetylcisteine is under discussion, taking into account the favourable risk profile of this drug, it seems reasonable to administer N-acetylcisteine in addition to saline administration. In ACS patients with severe RF, the risk of severe bleeding depends upon the anticoagulation regimen, increasing particulary when unfractionated heparin is used in combination with GP IIb/IIIa inhibitors.

J Endourol. 2009 May 20; Malcolm JB, Berry TT, Williams MB, Logan JE, Given RW, Lance RS, Barone B, Shaves S, Vingan H, Fabrizio MDAbstract Background and Purpose: While partial nephrectomy remains the gold standard for the management of most small renal masses, increasing experience with renal cryoablation has suggested a viable alternative with a favorable morbidity profile and good efficacy. We report intermediate-term oncologic outcomes from a single-center experience with laparoscopic and percutaneous renal cryoablation. Patients and Methods: We performed a retrospective review of our laparoscopic renal cryoablation (LRC) and percutaneous renal cryoablation (PRC) experience between January 2003 and April 2007. Patients with at least 12 months of follow-up were included in the analysis. Follow-up consisted of imaging and laboratory studies at regular intervals. Persistent mass enhancement or interval tumor growth was considered a treatment failure. Results: Sixty-six patients (44% women/56% men; 42% African-American/58% Caucasian/other; mean body mass index, 29.7) with 72 tumors underwent either LRC (n = 52) or PRC (n = 20) with a mean follow-up of 30 months (median 25.1 mos; range 13-63 mos). Average patient age was 66.5 years (range 34-82 yrs). Mean tumor size was 2.33 cm (range 1-4.6 cm). Comorbid conditions were prevalent: 76% hypertension, 36% hyperlipidemia, 24% chronic kidney disease, 29% diabetes mellitus, 36% tobacco use, and 32% heart disease. Results of pretreatment biopsy were 62% renal-cell carcinoma and 38% benign or nondiagnostic. Overall cancer-specific and cancer-free survival were 100% and 97%, respectively. There were two treatment failures (3.8%) in the LRC group and five primary failures in the PRC group (25%) (P = 0.015), four of which were salvaged with repeated PRC with no evidence of recurrence at 6 to 36 months of follow-up. There has been no significant local or metastatic progression. Conclusions: LRC and PRC achieved good oncologic control with minimal morbidity at a mean follow-up of 30 months in a patient cohort characterized by numerous comorbid conditions. PRC had a significantly higher primary treatment failure rate than LRC, but re-treatment offered salvage oncologic control with no significant complications.

J Adv Nurs. 2009 Apr 30; Luttik ML, Jaarsma T, Lesman I, Sanderman R, Hagedoorn Mluttik m.l., jaarsma t., lesman i., sanderman r. & hagedoorn m. (2009) Quality of life in partners of people with congestive heart failure: gender and involvement in care. Journal of Advanced NursingAbstract Title. Quality of life in partners of people with congestive heart failure: gender and involvement in care. Aim. This paper is a report of a study conducted to investigate quality of life in partners of people with congestive heart failure in comparison to individuals living with a healthy partner. Background. Congestive heart failure is a chronic debilitating disease with severe symptoms and complex treatment. The support of partners is essential in the management of congestive heart failure. Living with a chronic illness generally affects the quality of life of patients and their partners. Method. Data were collected using a cross-sectional, comparative design between October 2002 and February 2005 with 303 partners of people with congestive heart failure. Reference data were collected in 304 age- and gender-matched individuals living with a healthy partner, drawn from the general population. All respondents completed questionnaires at home on quality of life and general well-being. Analysis of variance was used to analyse the data. Findings. Overall, differences in quality of life between partners of people with heart failure and matched controls were small. However, substantial variation in the quality of life of partners was found by exploring the role of gender and involvement in care. Quality of life scores varied strongly for male and female partners who had to perform caregiving tasks. The performance of these caregiving tasks was negatively associated with the quality of life of female partners but not with that of male partners. Conclusion. Female partners especially should not be overlooked when they become involved in personal care tasks. Nurses should not be reluctant to involve male partners in caring for women with heart failure.

J Hypertens. 2009 May 15; Costanzo P, Perrone-Filardi P, Petretta M, Marciano C, Vassallo E, Gargiulo P, Paolillo S, Petretta A, Chiariello MOBJECTIVE: The aim of this study was to assess the effect of calcium channel blocker (CCB) treatment, compared with other drugs or placebo/top of therapy, on all-cause mortality, cardiovascular death, major cardiovascular events, heart failure, myocardial infarction and stroke. METHODS: We performed a meta-analysis of randomized controlled trials that compared a long-acting calcium channel blocker with another drug or placebo/top of therapy and that assessed all-cause mortality and cardiovascular events. RESULTS: We included 27 trials (175 634 patients). The risk of all-cause death was reduced by dihydropyridine CCBs [odds ratio (OR) 0.96; 95% confidence interval (CI) 0.93-0.99; comparison P = 0.026; heterogeneity P = 0.87)] without influence of placebo trials. The risk of heart failure was increased by CCBs compared with active treatment (OR 1.17; 95% CI 1.11-1.24; comparison P = 0.0001; heterogeneity P = 0.0001), and it was decreased when compared with placebo (OR 0.72; 95% CI 0.59-0.87; comparison P = 0.001; heterogeneity P = 0.77), also in the subgroup of coronary artery disease patients (OR 0.76; 95% CI 0.61-0.95; comparison P = 0.01; heterogeneity P = 0.29). CCBs did not increase the risk of myocardial infarction (OR 1; 95% CI 0.95-1.04; comparison P = 0.83, heterogeneity P = 0.004), cardiovascular death (OR 0.97; 95% CI 0.93-1.02; comparison P = 0.24; heterogeneity P = 0.16), major cardiovascular events (OR 0.97; 95% CI 0.90-1.06; comparison P = 0.53; heterogeneity P = 0.0001). CCBs decreased the risk of fatal or nonfatal stroke (OR 0.86; 95% CI 0.82-0.90; comparison P = 0.0001, heterogeneity P = 0.12), also, when compared with angiotensin-converting enzyme inhibitors (OR 0.87; 95% CI 0.78-0.97; comparison P = 0.016; heterogeneity P = 0.48). CONCLUSION: Our study demonstrates that CCBs reduce the risk of all-cause mortality compared with active therapy and prevent heart failure compared with placebo. Furthermore, with the inclusion of recent trials, we confirm that they reduce the risk of stroke, also in comparison to angiotensin-converting enzyme inhibitors and do not increase the risk of cardiovascular death, myocardial infarction and major cardiovascular events.

Br J Dermatol. 2009 May 12; Jidar K, Ingen-Housz-Oro S, Beylot-Barry M, Paul C, Chaoui D, Sigal-Grinberg M, Morel P, Dubertret L, Bachelez HBackground Primary cutaneous T-cell lymphomas (CTCLs) are malignancies characterized by a clonal T-cell infiltrate involving the skin. CTCLs often show resistance to conventional antineoplastic chemotherapy. Gemcitabine is a pyrimidine analogue which has shown efficacy and a favourable safety profile in solid tumours and haematological malignancies. Objectives We report a multicentre retrospective study of 23 patients who received gemcitabine for advanced-stage CTCL and emphasize the high incidence of serious unusual adverse events. Methods We collected data from 23 patients with refractory CTCL (14 mycosis fungoides, six Sézary syndrome and three other CTCL). Gemcitabine was given weekly within a 21- or 28-day schedule. Response was evaluated after three and six cycles of chemotherapy. For each patient, all adverse events were recorded. Results Of the 16 patients who received at least three cycles of gemcitabine, 10 achieved a response (62.5%). Only five patients reached the sixth cycle of treatment and four still had a favourable response. Haematological toxicity was recorded in 15 cases with severe grade 3 or 4 neutropenia in seven patients (30%) and six serious infections (26%). Other serious adverse events were observed in six cases (26%): one haemolytic-uraemic syndrome, one severe capillary leak syndrome, one acute heart failure related to cardiac arrhythmia, two bullous and erosive dermatitis, and one recurrent influenza-like syndrome with altered general condition. Conclusions Our study confirms the early efficacy of gemcitabine in advanced-stage CTCL. However, our results contradict the safety profile of gemcitabine previously reported and underline the high incidence of severe complications including visceral and cutaneous involvement.

Med Care. 2009 May 8; Braithwaite RS, Fiellin D, Justice ACBACKGROUND:: Practice guidelines rarely consider comorbid illness, and resulting overuse of health services may increase costs without conferring benefit. OBJECTIVE:: To individualize a framework for inferring when patients with comorbid illness are not likely to benefit from colorectal cancer screening guidelines. METHODS:: We modified the "payoff time" framework (the minimum time until a guideline's cumulative benefits exceed its cumulative harms) to increase its applicability to a wide range of primary care patients. We show how it may inform colorectal (CR) cancer screening decisions for 3 typical patients in general practice for whom CR screening would be recommended by current guidelines: (1) 60-year-old man with diabetes, congestive heart failure, lung disease, stroke, and substantial frailty; (2) 60-year-old woman with diabetes and obesity, without other comorbidity or frailty; and (3) 50-year-old woman with inflammatory bowel disease. RESULTS:: For patient 1, the payoff time for CR screening (minimum time until benefits exceed harms) is 7.3 years, and for patient 2, the payoff time for CR screening is 5.4 years. Evidence is insufficient to estimate the payoff time for patient 3. Because patient 1's estimated life expectancy is 3.7 years (less than his payoff time), he is unlikely to benefit from CR screening. Because patient 2's estimated life expectancy exceeds 10 years (greater than her payoff time), she may benefit from CR screening. Because evidence is insufficient to estimate the payoff time for patient 3, the payoff time framework does not inform decision making. CONCLUSION:: The payoff time framework may identify patients for whom particular clinical guidelines are unlikely to confer benefit, and has the potential to decrease unnecessary health care.

Int J Clin Exp Med. 2009; 2(1): 76-86Robinson P, Garza A, Moore J, Eckols TK, Parti S, Balaji V, Vallejo J, Tweardy DJMyocarditis is an important cause of heart failure in adolescents and young adults and is caused, most commonly, by viral infections. Viral myocarditis is characterized by cardiac inflammation and cardiomyocyte necrosis. The molecular pathogenesis of viral myocarditis is incomplete and specific therapies are not available. Proinflammatory cytokines such as IL-1beta, TNF-alpha and IL-6 have been implicated in the pathogenesis of myocarditis caused by encephalomyocarditis virus (EMCV) infection, a model of viral myocarditis in mice. Substance P (SP), a neuropeptide and pain transmitter, stimulates the production of proinflammatory cytokines and has been demonstrated by us and others to contribute to the pathogenesis of several viral, protozoan and helminth infections in mouse and man. Receptors for SP are expressed on the surface of cardiomyocytes, neurons, endothelial cells and immunocytes, including lymphocytes and macrophages. The current studies were performed to evaluate the role of SP in the pathogenesis of EMCV-induce myocarditis. SP levels were increased 61 fold in EMCV infected wild-type mice. EMCV infection resulted in 51% mortality at 14 days and a 1.56 fold increase in heart-to-body weight ratio that was accompanied by cardiac inflammation and necrosis and along with cardiomyocyte apoptosis and hypertrophy of surviving cells. In contrast, SP precursor knockout mice were completely protected from EMCV-mortality, cardiomegaly, cardiac inflammation and necrosis as well as cardiomyocyte apoptosis and hypertrophy. These results indicate that SP is essential for the pathogenesis of EMCV myocarditis and suggest that targeting this signaling pathway may be beneficial in viral myocarditis in humans.

J Cardiovasc Med (Hagerstown). 2009 May; 10(5): 433-42Marziliano N, Grasso M, Pilotto A, Porcu E, Tagliani M, Disabella E, Diegoli M, Pasotti M, Favalli V, Serio A, Gambarin F, Tavazzi L, Klersy C, Arbustini EWhole gene expression analysis through microarray technologies revolutionized the manner of identifying changes in biological events and complex diseases, such as cardiovascular settings. These new methodologies may scan up to 35 000 transcripts at once rather than screening a small amount of genes one at a time. The ability of microarrays to provide a broad insight into the disease process directly within the tissues provides a unique insight into the intracellular perturbations of the cell organization and function and sheds an entirely unique new perspective on the heart failure process. Commonalities and differences at the molecular level will identify critical pathways of pathogenesis, and response to therapy, or both: indeed, gene expression profiling holds tremendous promise for classifying clinical phenotypes, developing prognostic predictors and, most importantly, providing novel unbiased insights into the mechanisms underlying heart disease and, eventually, novel causative genes. On the contrary, established proteomic technologies, together with the new alternative strategies currently under evaluation (i.e. metabolomics), are now making possible the translation of data obtained on the bench to the daily clinical routine with the discovery of new diagnostic/prognostic biomarkers (such as troponin for ACS and BNP for congestive heart failure) and the identification of new therapeutic approaches for combating heart diseases. Finally, genomic studies (including transcriptomics) together with proteomics should not represent a challenge for who is going to win the final battle, but rather they should provide a setting in which together and in a complementary fashion the final fight against heart disease can be won.

Rev Port Cardiol. 2009 Feb; 28(2): 143-54Silva-Cardoso J, Ferreira J, Oliveira-Soares A, Martins-de-Campos J, Fonseca C, Lousada N, Ilídio-Moreira J, Rabaçal C, Damasceno A, Amorim S, Seabra-Gomes R, Ferreira R, Abreu-Lima C, BACKGROUND: In previous randomized studies levosimendan improved hemodynamics and clinical course, with a still unclear effect on prognosis. There are, however, few data regarding its effects when used in daily practice. AIMS: We evaluated the clinical effectiveness and safety of levosimendan in the treatment of acute systolic heart failure (SHF) in daily practice conditions. METHODS: In this prospective, multicenter, nonrandomized trial, a continuous infusion of levosimendan (0.05 microg/kg/min-0.2 microg/kg/min) was administered for 24 hours. An optional loading dose of 12 microg/kg over 10 minutes was used. The primary combined endpoint of clinical effectiveness (as defined by a eight-variable clinical score) and safety (defined by the absence of serious adverse events) was assessed at 24 hours after the beginning of treatment; a second similar primary combined endpoint was assessed at 5 days. RESULTS: One hundred and twenty-nine consecutive patients requiring inotropes despite optimal oral background heart failure therapy were recruited. The primary endpoint was reached in 80.6% at 24 hours and in 79.7% at 5 days. During the six months before levosimendan the number of patient days of hospitalization for heart failure was 14.9 +/- 14.6 versus 3.1 +/- 7.6 during the six months following levosimendan (p < 0.001). CONCLUSIONS: In daily practice, levosimendan was clinically effective and safe in 80.6% and 79.7% of patients with acute SHF at 24 hours and 5 days respectively after the beginning of treatment. A marked reduction in the number of days of hospitalization for heart failure was also seen during the subsequent six months.

Arch Intern Med. 2009 May 11; 169(9): 851-7Levitan EB, Wolk A, Mittleman MABACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet effectively reduces blood pressure. In observational studies, the association between diets consistent with DASH and risk of coronary heart disease and stroke has been examined with varying results. We hypothesized that diets consistent with the DASH diet would be associated with a lower incidence of heart failure (HF). METHODS: We conducted a prospective observational study in 36 019 participants in the Swedish Mammography Cohort who were aged 48 to 83 years and without baseline HF, diabetes mellitus, or myocardial infarction. Diet was measured using food-frequency questionnaires. We created a score to assess consistency with the DASH diet by ranking the intake of DASH diet components and 3 additional scores based on food and nutrient guidelines. Cox proportional hazards models were used to calculate rate ratios of HF-associated hospitalization or death, determined using the Swedish inpatient and cause-of-death registers between January 1, 1998, and December 31, 2004. RESULTS: During 7 years, 443 women developed HF. Women in the top quartile of the DASH diet score based on ranking DASH diet components had a 37% lower rate of HF after adjustment for age, physical activity, energy intake, education status, family history of myocardial infarction, cigarette smoking, postmenopausal hormone use, living alone, hypertension, high cholesterol concentration, body mass index (calculated as weight in kilograms divided by height in meters squared), and incident myocardial infarction. Rate ratios (95% confidence intervals) across quartiles were 1 [Reference], 0.85 (0.66-1.11), 0.69 (0.54-0.88), and 0.63 (0.48-0.81); P(trend) < .001. A similar pattern was seen for the guideline-based scores. CONCLUSION: In this population, diets consistent with the DASH diet are associated with lower rates of HF.

Jt Comm J Qual Patient Saf. 2009 Apr; 35(4): 199-205Bader MK, Neal B, Johnson L, Pyle K, Brewer J, Luna M, Stalcup C, Whittaker M, Ritter MBACKGROUND: From 2003-2005, a comprehensive review of all cardiac/respiratory arrests at Mission Hospital (Mission Viejo, California) uncovered deficits in knowledge and judgment in the hours preceding 75% of our non-ICU patients. Nearly half of all arrests were occurring outside the ICU, with an overall mortality rate of 60%. In addition, transfers into ICU from the floor averaged 96 patients per month. METHODS: A multidisciplinary team met for 12 months to develop a specialized nurse-driven rapid response team (RRT) to reduce the incidence and mortality of non-ICU arrests, reduce transfers to the ICU from the floor, and provide ICU-level nursing care for emergency department (ED) patients in extremis. The team developed an RRT protocol, a methodology for rounds and calls, and a data collection system. After gaining consensus among the nursing managers, 4.2 full-time equivalent (FTE) RRT nurse positions were created by each unit contributing portions of an FTE. RESULTS: Prospective data collected demonstrated an inpatient call frequency averaging 118 calls per 1,000 discharges; 138 calls per month were in support of the ED. Floor codes were reduced from 36 to 17 per year, and the mortality rate in the floor-code patients decreased from 61% to 26%. Unanticipated transfers from the floor units to the ICU decreased significantly. DISCUSSION: The RRT initiative delivered measurable outcomes demonstrating the hospital's commitment to saving the vulnerable hospitalized patient population. In addition, the identification of critical system and clinical issues resulted in efforts to improve processes and identify patient subpopulations at risk (for example, patients with congestive heart failure, end-stage heart disease, high-dose narcotics).

J Formos Med Assoc. 2009 May; 108(5): 353-66Chang LC, Huang KC, Wu YW, Kao HL, Chen CL, Lai LP, Hwang JJ, Yang WSAdipose tissue is now accepted by the scientific and medical community to be a genuine endocrine organ, in addition to its classical role as an energy store. Adiponectin is one of the many adipocytokines that are secreted almost exclusively by adipose tissue. Alteration in blood adiponectin concentrations has been linked to many human diseases in numerous cross-sectional and prospective studies. In this review, we describe briefly the biological effects of adiponectin as revealed by basic scientific investigations. We also summarize the principles of blood adiponectin assays. Overall, lower blood adiponectin concentration is found in subjects with obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension. These medical conditions are components of the metabolic syndrome and major risk factors for accelerated atherosclerosis. Plasma adiponectin levels are also expected to be lower in subjects with cardiovascular diseases, such as coronary artery disease, ischemic stroke and peripheral artery disease. Congestive heart failure (CHF) and cardiac arrhythmia are common end points in cardiovascular diseases. Surprisingly, higher blood adiponectin levels are frequently reported to predict mortality associated with CHF. Few human data regarding adiponectin and cardiac arrhythmia are available. Higher blood adiponectin level has been documented only in atrial fibrillation. We also summarize data on the role of the high molecular weight (HMW) isoforms of adiponectin and the effects of clinical treatment on the levels of total or HMW adiponectin. Whether adiponectin is a risk marker or a risk factor for the diseases reviewed in this article, and in many other human diseases, and their detailed pathogenic links awaits further investigation.

Adv Ther. 2009 May 14; Fabbri G, Maggioni APAbundant evidence from large-scale clinical trials supports the importance of lowering low-density lipoprotein cholesterol (LDL-C) to decrease the risk of cardiovascular disease (CVD) events. The LDL-C targets in various guidelines remain important treatment goals but, even in trials where statin therapy achieves substantial reduction of LDL-C, a significant number of CVD events still occur and the residual risk remains high. These findings suggest that lipid parameters other than LDL-C, such as high-density lipoprotein cholesterol (HDL-C), triglycerides, and LDL particle size, can influence the risk of CVD. On this basis, other strategies that can alter the lipid profile, in particular raising HDL.C, may provide additional benefits. Other factors such as HDL-C functionality and susceptibility to oxidation and inflammatory factors can also influence cardiovascular risk. In addition to the modifications of the lipid profile, statins have cholesterolindependent beneficial pleiotropic effects. The contribution of these effects to event reduction is not yet fully understood. Recently, the body of evidence has expanded to support the use of intensive statin therapy in broader patient populations. The JUPITER trial has shown the benefit of intensive statin treatment in low-risk subjects with high levels of high-sensitivity C-reactive protein and average levels of LDL-C. Unlike the setting of primary and secondary prevention, the results of statin trials in patients with heart failure have shown no clear benefit in terms of survival. The recently published AURORA trial was carried out to investigate the effect of rosuvastatin in patients with end-stage renal disease undergoing chronic hemodialysis. In this trial no benefit on cardiovascular events was shown with statin therapy. In conclusion, large outcomes trials have clearly shown that statin treatments have a favorable benefit/risk profile in a large range of patients at different levels of risk, with the exception of patients with heart failure and those with renal disease undergoing dialysis. Further evidence is needed on the role of therapeutic strategies on the so-called residual risk.

Herz. 2009 May; 34(3): 198-205Denk K, Vahl CFBACKGROUND: : Treatment of infective endocarditis is primarily conservative. Persistent infection, tissue destruction und hemodynamic instabilities argue - in dependence on the microorganisms involved - for an urgent surgical treatment, even when there is still no control of the local and systemic infection. For timing of the surgical intervention, the following suggestions seem to be valid: TIMING OF THE SURGICAL INTERVENTION: : Delayed surgical indication is considered a prognostic factor of extraordinary relevance for surgical treatment of infective endocarditis. Presence of intramyocardial, paravalvular and root abscess or development of a septic cardiomyopathy (in addition to the valve-related disturbed pump and muscular function), systemic sepsis and irreversible extracardiac organ destruction (liver, spleen, kidney, brain, lung, bone, etc.) reduce the surgical prognosis even after successful and complete surgical treatment. Extracardiac foci may determine the postoperative course. After cerebral embolization the cardiac operation should be performed as early as possible (within 24-48 h after embolization). Extreme extent of cardiac and extracardiac tissue destruction due to delayed surgical indication can result in a situation, where adequate surgical treatment of the local focus is not likely to be successful anymore and prognosis becomes infaust. In their own patients, the authors observed: NYHA (New York Heart Association) III-IV > 50%; renal failure (dialysis) > 15%, systemic embolization > 30%, cerebral embolization > 8%, cardiogenic shock > 10%. SURGICAL TREATMENT: : The most important aspect is complete debridement of all infected tissue with a safety margin of about 3 mm. This holds true, even if it results in resection of the entire aortic root, mitral ring, aortic wall, and atrial tissue. There is no contraindication to the implantation of prosthetic materials (valves, bovine pericardium, mitral rings) as long as surgical debridement has been prompt and aggressive. Not the type of prosthesis, but the quality of surgical debridement is of prognostic relevance. Reconstructive techniques are suggested whenever possible and are primarily effective for the treatment of mitral and tricuspid valves. Prompt and aggressive eradication of extracardiac foci is important to the patient's postoperative course. POSTOPERATIVE COURSE AND TIMING OF THE OPERATION: : After successful surgical treatment of the intracardiac focus, the postoperative course is mainly determined by extracardiac foci, systemic sepsis, and persistent secondary organ destruction. PERSPECTIVE: : As the results of conservative treatment of infective endocarditis are still not satisfactory, in some subgroups improved surgical results due to aggressive and radical debridement of infective tissue (with a safety margin of at least 3 mm) will suggest the surgical treatment option even in those patients, that have primarily been considered for conservative treatment.

J Physiol Pharmacol. 2009 Mar; 60(1): 61-8Goraca A, Piechota A, Huk-Kolega HLipopolysaccharide (LPS) is a gram-negative bacterial endotoxin and a major factor that contributes to multiple organ failure, including heart injury. Myocardial dysfunction in septic shock depends on the presence of proinflammatory cytokines and reactive oxygen/nitrogen species. In this study, the effect of early administration of an antioxidant, alpha-lipoic acid (LA) on lipid peroxidation, hydrogen peroxide (H(2)O(2)), sulphydryl groups (-SH groups) and total protein concentration and the glutathione redox system was evaluated in the heart homogenates obtained from LPS-induced endotoxic shock rats (Escherichia coli 026:B6, 30 mg/kg, i.v.). The animals were treated intravenously with saline or LA (60 mg/kg or 100 mg/kg i.v.) 30 min after LPS injection. Five hours after LPS, LA or saline administration, the animals were sacrificed and their hearts were isolated for measurements. Injection of LPS alone resulted in the development of shock and oxidative stress that was indicated by a significant increase in thiobarbituric acid reactive substances (TBARS) and H(2)O(2) concentrations, a decrease in concentration of -SH groups and reduced glutathione, and by decrease in glutathione redox ratio reduced glutathione (GSH)/oxidized glutathione (GSSG) in the heart. Administration of LA after the LPS challenge resulted in an increase in the sulfhydryl group content and a decrease in TBARS and H(2)O(2) concentrations in the heart as compared with the LPS group. In addition, the treatment of LA after LPS challenge significantly decreased the level of GSSG, increased the level of GSH in heart homogenates resulting in an increase of the GSH/GSSG ratio compared with the LPS group. There was no difference in oxidative stress reduction between 60 mg/kg and 100 mg/kg doses. These results indicate that early administration of LA is highly effective in dampening endotoxin-induced oxidative stress in the heart and in improving the glutathione redox system. This study supports the idea that alpha-LA is a free radical scavenger and a potent antioxidant.

World J Surg. 2009 May 14; Liu YY, Yeh CN, Lee HL, Chu PH, Jan YY, Chen MFBACKGROUND: Cardiovascular disease (CVD) and gallstones are reported to be strongly associated because both diseases are frequently part of a metabolic syndrome. Laparoscopic cholecystectomy (LC) has become the standard treatment for gallbladder disease around the world. Cardiovascular disease is considered as an absolute or relative contraindication for LC; however, clinical information regarding the applicability of LC for treating gallbladder disease in CVD patients is lacking. This study aims to assess the suitability of LC for the treatment of gallbladder disease in CVD patients. METHODS: The medical records of 66 patients with severe CVD (including valvular heart disease, ischemic heart disease, and heart failure) and gallbladder disease (CVD-group) who underwent LC between 1966 and 2005 were retrospectively reviewed. Furthermore, these data were compared with the clinical features and outcomes of 8,834 patients with gallbladder disease who underwent LC but did not have severe CVD (NCVD-group). RESULTS: Of the 8,900 patients with gallbladder disease undergoing LC, the 66 (0.74%) who comprised the CVD-group clearly exhibited advanced age, male predominance, higher blood urea nitrogen (BUN) levels, and a longer duration of hospitalization as compared with the NCVD-group patients. A longer duration of hospitalization and a higher incidence of acute cholecystitis and chronic cholecystitis were identified as independent factors differentiating the CVD-group patients, who had previously undergone open-heart surgery, from the NCVD-group patients who underwent LC. For the CVD-group patients, adjustment of anticoagulant therapy contributed to the longer duration of hospitalization, but postoperative complications did not. Advanced age and male predominance were identified as independent factors differentiating the patients who developed ischemic heart disease that required intervention from the NCVD-group patients undergoing LC. The operative morbidity and mortality rates of LC are likely to be similar when it is used to treat selected patients with severe CVD and gallbladder disease and when it is used to treat patients with gallbladder disease and no CVD. CONCLUSIONS: Laparoscopic cholecystectomy is a suitable procedure for treating selected patients with severe CVD and gallbladder disease, and its operative morbidity and mortality rates are similar in these patients and in patients with gallbladder disease alone. Nevertheless, appropriate preoperative preparations and established operative techniques in the hands of an experienced surgeon are mandatory.

J Card Surg. 2009 May-Jun; 24(3): 269-74Yerebakan C, Ugurlucan M, Bayraktar S, Bethea BT, Conte JVBACKGROUND: Lung transplantation offers an established therapeutic option for end-stage lung disease. It is associated with several complications, and early allograft failure is one of the most devastating among all. Different studies are focused on an attempt to minimize these complications, especially transplant failure. We aimed to evaluate the effects of inhaled nitric oxide (iNO) treatment in patients receiving lung transplantation. METHODS: Nine patients (six female, three male; mean age 42.9 +/- 15.8) requiring lung transplantation for end-stage pulmonary disease--chronic obstructive pulmonary disease (three patients), cystic fibrosis (three patients), scleroderma and systemic sclerosis (two patients), Eisenmenger's syndrome (one patient), and treated with iNO were included in this retrospective study. Hemodynamic data (mean arterial pressure, mean pulmonary arterial pressure, heart rate) and respiratory parameters were analyzed. Pretreatment data were compared with the post-iNO treatment data at 6-8 hours and 12-14 hours. RESULTS: The inhalation of nitric oxide was started with an initial dose of 40 parts per million (ppm) and the dose was gradually decreased until hemodynamic and pulmonary stability was achieved. Six patients underwent double-lung transplantation and three single-lung transplantations were performed. Cardiopulmonary bypass was used in seven patients. The iNO therapy was started before transplantation in five patients, after the procedure in four patients. Mean iNO therapy duration was 83.2 +/- 74.4 hours. The administration of iNO resulted in a significant reduction in mean pulmonary arterial pressure (36.8 +/- 15.8 mm Hg to 22 +/- 6.8 mm Hg at 6-8 hours and 22.8 +/- 7.96 mm Hg at 12-14 hours). Mean systemic arterial pressure slightly increased at 6-8 hours and significantly increased at 12-14 hours (70.2 +/- 6.3 mm Hg to 90.1 +/- 11.96 mm Hg). Heart rate was not significantly affected with the treatment. Arterial oxygenation improved with the treatment. All patients except one showed improvement of overall respiratory functions. The mean duration of mechanical ventilation was 12.8 +/- 10.9 days. Mortality occurred in one patient due to neurologic injury. NO(2) and methemoglobin levels were closely monitored during the treatment. Methemoglobinemia did not occur and NO(2) levels remained between 0.1 and 0.4 ppm. CONCLUSION: Nitric oxide inhalation for the prevention and treatment of early allograft failure in lung transplant recipients is encouraging. It is superior to other vasodilators with its selectivity to the pulmonary vasculature, while having no significant side effects on systemic circulation. It appears to improve gas exchange and oxygenation properties. Further prospective randomized studies will aid to standardize inhalation nitric oxide therapy.

Cardiol J. 2009; 16(3): 254-8Carvalho VO, Pascoalino LN, Bocchi EA, Ferreira SA, Guimarães GVBackground: One way of defining an individual's heart effort is to calculate the maximum heart rate to be expected given their age, but the reinnervation seen in patients who have received heart transplants makes for different calculations from patients who have suffered heart failure. The purpose of this study is to evaluate heart rate dynamics (rest, peak and percentage of predicted heart rate for age) in heart transplant patients compared to optimized beta-blocked heart failure patients during a treadmill cardiopulmonary exercise test. Methods: Twenty two (81% male, 46 +/- 12 years) sedentary heart failure patients and 15 (47% male, 44 +/- 13 years) sedentary heart transplant patients performed a treadmill cardiopulmonary exercise test between 10 am and 3 pm. Heart failure optimization was considered 50 mg/day or more of carvedilol, with a resting heart rate of between 50 and 60 bpm. Results: Basal heart rate was lower in heart failure patients (58 +/- 5 bpm) compared to heart transplant patients (93 +/- 11 bpm; p < 0.0001). Similarly, the peak heart rate (percentage of the maximum predicted for age) was lower in heart failure patients (60 +/- 13%) compared to heart transplant patients (80 +/- 12; p < 0.0001). Maximum respiratory exchange ratio did not differ between the groups (1.05 +/- 0.06 in heart failure patients and 1.11 +/- 0.1 in heart transplant patients; p = 0.08). Moreover, the heart rate reserve between heart failure (49 +/- 22) and heart transplantation (46 +/- 16%) was not different (p = 0.644). Conclusions: No patient reached the maximum heart rate predicted for their age during a treadmill cardiopulmonary exercise test. The heart rate reserve was similar between groups. A heart rate increase in heart transplant patients during cardiopulmonary exercise test of more than 80% of the maximum age-adjusted value should be considered an effort near the maximum.

Cardiol J. 2009; 16(3): 218-26Trojnarska O, Grajek S, Kramer L, Gwizdała ABackground: Supraventricular arrhythmia (SVA) is a frequent clinical complication in adult patients with congenital heart disease (CHD). The aim of this study is prognostic evaluation of congenital heart defect complexity, performed cardiac surgery, initial functional impairment of the heart - NYHA > I, cyanosis, age and sex of the adult patients with CHD, presenting for the first time to an outpatient clinic, on SVA occurrence during long-term observation. Methods: We looked at 1,304 patients (586 men), aged 18-72 years (mean 29.4 +/- 10.6 years), and followed-up from 1995 to 2004. The mean observation period was 3.52 +/- 1.83 years. SVA in the form of atrial flutter/fibrillation (FA/FLA) and supraventricular tachycardia was observed in 133 patients, 10.3% of the study population. Ten-year follow-up showed that the likelihood of SVA occurrence in the whole studied population after two years was 5.2%, and 14.4% after ten years. Results: Univariate analysis proved that the incidence of SVA is greater in patients with complex heart defects (p = 0.0001), those not previously operated upon (p = 0.0001), those with baseline impairment of cardiac function (NYHA > I; p = 0.0001) and those with cyanosis (0.0001). The patient's sex seems to have little significance. Cox regression analysis showed that baseline heart failure is the strongest risk factor for SVA (HR = 4.66). Congenital heart defect complexity (HR = 2.31) and the patient's age are also significant prognostic factors of this arrhythmia (HR = 1.32). Cardiac surgery, cyanosis and patient sex are not significant in prognosis. Conclusions: Baseline impairment of heart function, heart defect complexity and patient's age all increase the risk of SVA in the population of adults with congenital heart disease. Cyanosis and the lack of cardiac surgery in the past led to a higher incidence of the analyzed arrhythmia but are not risk factors for its occurrence. Gender has no prognostic significance for SVA.

JAMA. 2009 May 13; 301(18): 1892-901Jankowska EA, Rozentryt P, Ponikowska B, Hartmann O, Kustrzycka-Kratochwil D, Reczuch K, Nowak J, Borodulin-Nadzieja L, Polonski L, Banasiak W, Poole-Wilson PA, Anker SD, Ponikowski PCONTEXT: Androgen deficiency is common in men with chronic heart failure (HF) and is associated with increased morbidity and mortality. Estrogens are formed by the aromatization of androgens; therefore, abnormal estrogen metabolism would be anticipated in HF. OBJECTIVE: To examine the relationship between serum concentration of estradiol and mortality in men with chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study at 2 tertiary cardiology centers (Wroclaw and Zabrze, Poland) of 501 men (mean [SD] age, 58 [12] years) with chronic HF, LVEF of 28% (SD, 8%), and New York Heart Association [NYHA] classes 1, 2, 3, and 4 of 52, 231, 181, and 37, respectively, who were recruited between January 1, 2002, and May 31, 2006. Cohort was divided into quintiles of serum estradiol (quintile 1, < 12.90 pg/mL; quintile 2, 12.90-21.79 pg/mL; quintile 3, 21.80-30.11 pg/mL; quintile 4, 30.12-37.39 pg/mL; and quintile 5, > or = 37.40 pg/mL). Quintile 3 was considered prospectively as the reference group. MAIN OUTCOME MEASURES: Serum concentrations of estradiol and androgens (total testosterone and dehydroepiandrosterone sulfate [DHEA-S]) were measured using immunoassays. RESULTS: Among 501 men with chronic HF, 171 deaths (34%) occurred during the 3-year follow-up. Compared with quintile 3, men in the lowest and highest estradiol quintiles had increased mortality (adjusted hazard ratio [HR], 4.17; 95% confidence interval [CI], 2.33-7.45 and HR, 2.33; 95% CI, 1.30-4.18; respectively; P < .001). These 2 quintiles had different clinical characteristics (quintile 1: increased serum total testosterone, decreased serum DHEA-S, advanced NYHA class, impaired renal function, and decreased total fat tissue mass; and quintile 5: increased serum bilirubin and liver enzymes, and decreased serum sodium; all P < .05 vs quintile 3). For increasing estradiol quintiles, 3-year survival rates adjusted for clinical variables and androgens were 44.6% (95% CI, 24.4%-63.0%), 65.8% (95% CI, 47.3%-79.2%), 82.4% (95% CI, 69.4%-90.2%), 79.0% (95% CI, 65.5%-87.6%), and 63.6% (95% CI, 46.6%-76.5%); respectively (P < .001). CONCLUSION: Among men with chronic HF and reduced LVEF, high and low concentrations of estradiol compared with the middle quintile of estradiol are related to an increased mortality.

Ann Acad Med Singapore. 2009 Apr; 38(4): 309-6Sivathasan CIntroduction: The status of heart transplantation in Singapore is reviewed in this article. Materials and Methods: The database of 40 consecutive heart transplantations from July 1990 through December 2007 is reviewed retrospectively. The data is compared with the 2008 registry data of the International Society for Heart and Lung Transplantation (ISHLT). Results: The average age of recipients was 45.3 years. Ages ranged from 14 to 64 years. Ischaemic cardiomyopathy (52.5%) and dilated cardiomyopathy (42.5%) were the major indications. From 1990 to 1999, 50% of the donors sustained brain death from road traffic accident, 25% from cerebrovascular accident and 25% from falling from height, whereas the cause of brain death in the donors from 2000 to 2007 was 33%, 47% and 9.5%, respectively. The average donor age increased from 28.3 to 38.1 years. The significant morbidities in the recipients were hypertension, cytomegalovirus (CMV) infection, cardiac allograft vasculopathy and renal dysfunction. Thirtytwo required treatment for hypertension. 67.5% developed CMV disease requiring treatment. Cardiac allograft vasculopathy was diagnosed in 10. Rising creatinine levels reaching over 2.5 mg/dL was seen in 7. Three required renal dialysis. Epstein-Barr virus related lympho proliferative disorder occurred in 2 patients. One patient developed adenocarcinoma of stomach. The 30-day mortality was 10% and half life was 10 years. Cardiac allograft vasculopathy and sepsis caused 41.7% of mortality each. 11.7% of the mortality was due to cerebrovascular accident. Conclusion: The status of heart transplantation in Singapore is comparable to the ISHLT registry data. Transplant provides excellent early survival of 80%; however, the expected half life is around 10 years after cardiac transplantation. The late mortality is mainly caused by cardiac allograft vasculopathy (CAV) and renal failure. More effort and research needs to be directed towards these issues to improve the long-term results.

Arch Intern Med. 2009 May 11; 169(9): 832-842Wright JT, Probstfield JL, Cushman WC, Pressel SL, Cutler JA, Davis BR, Einhorn PT, Rahman M, Whelton PK, Ford CE, Haywood LJ, Margolis KL, Oparil S, Black HR, Alderman MH, The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is reevaluated considering information from new clinical trials, meta-analyses, and recent subgroup and explanatory analyses from ALLHAT, especially those regarding heart failure (HF) and the association of drug treatment with new-onset diabetes mellitus (DM) and its cardiovascular disease (CVD) consequences. Chlorthalidone was superior to (1) doxazosin mesylate in preventing combined CVD (CCVD) (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.13-1.27), especially HF (RR, 1.80; 95% CI, 1.40-2.22) and stroke (RR, 1.26; 95% CI, 1.10-1.46); (2) lisinopril in preventing CCVD (RR, 1.10; 95% CI, 1.05-1.16), including stroke (in black persons only) and HF (RR, 1.20; 95% CI, 1.09-1.34); and (3) amlodipine besylate in preventing HF, overall (by 28%) and in hospitalized or fatal cases (by 26%). Central independent blinded reassessment of HF hospitalizations confirmed each comparison. Results were consistent by age, sex, race (except for stroke and CCVD), DM status, metabolic syndrome status, and renal function level. Neither amlodipine nor lisinopril was superior to chlorthalidone in preventing end-stage renal disease overall, by DM status, or by renal function level. In the chlorthalidone arm, new-onset DM was not significantly associated with CCVD (RR, 0.96; 95% CI, 0.88-2.42). Evidence from subsequent analyses of ALLHAT and other clinical outcome trials confirm that neither alpha-blockers, angiotensin-converting enzyme inhibitors, nor calcium channel blockers surpass thiazide-type diuretics (at appropriate dosage) as initial therapy for reduction of cardiovascular or renal risk. Thiazides are superior in preventing HF, and new-onset DM associated with thiazides does not increase CVD outcomes.

Hypertension. 2009 May 11; Lykke JA, Langhoff-Roos J, Sibai BM, Funai EF, Triche EW, Paidas MJMinimal data exist concerning the relationship between hypertensive pregnancy disorders and various subsequent cardiovascular events and the effect of type 2 diabetes mellitus on these. In a registry-based cohort study, we identified women delivering in Denmark from 1978 to 2007 with a first singleton (n=782 287) and 2 first consecutive singleton deliveries (n=536 419). The exposures were gestational hypertension and mild and severe preeclampsia. We adjusted for preterm delivery, small for gestational age, placental abruption, and stillbirth and, in a second model, we also adjusted for the development of type 2 diabetes mellitus. The end points were subsequent hypertension, ischemic heart disease, congestive heart failure, thromboembolic event, stroke, and type 2 diabetes mellitus. The risk of subsequent hypertension was increased 5.31-fold (range: 4.90 to 5.75) after gestational hypertension, 3.61-fold (range: 3.43 to 3.80) after mild preeclampsia, and 6.07-fold (range: 5.45 to 6.77) after severe preeclampsia. The risk of subsequent type 2 diabetes mellitus was increased 3.12-fold (range: 2.63 to 3.70) after gestational hypertension and 3.68-fold (range: 3.04 to 4.46) after severe preeclampsia. Women having 2 pregnancies both complicated by preeclampsia had a 6.00-fold (range: 5.40 to 6.67) increased risk of subsequent hypertension compared with 2.70-fold (range: 2.51 to 2.90) for women having preeclampsia in their first pregnancy only and 4.34-fold (range: 3.98 to 4.74) for women having preeclampsia in their second pregnancy only. The risk of subsequent thromboembolism was 1.03-fold (range: 0.73 to 1.45), 1.53-fold (range: 1.32 to 1.77), and 1.91-fold (range: 1.35 to 2.70) increased after gestational hypertension and mild and severe preeclampsia, respectively. Thus, hypertensive pregnancy disorders are strongly associated with subsequent type 2 diabetes mellitus and hypertension, the latter independent of subsequent type 2 diabetes mellitus. The severity, parity, and recurrence of these hypertensive pregnancy disorders increase the risk of subsequent cardiovascular events.

J Cardiovasc Med (Hagerstown). 2009 Apr; 10(4): 344-348Rapacciuolo A, Losi MA, Borgia F, De Angelis MC, Esposito F, Cavallaro M, De Rosa R, Piscione F, Chiariello MA 70-year-old man was admitted because of a 6-month history of progressive dyspnoea on exertion. The medical history showed that he suffered from patent ductus arteriosus (PDA) that was closed at 35 years of age by surgical ligation. Subsequently, up to year 1992, no evidence of residual left-to-right shunt was found. When he first came to our attention, we performed an echocardiographic test evidencing left ventricular dilation and contractile dysfunction and a recurrence of PDA. To exclude other possible causes of congestive heart failure, we performed several tests, including a coronary angiogram that showed coronary atherosclerosis without significant lesions. The haemodynamic study confirmed that the PDA was associated with a mild pulmonary hypertension with a QP: QS of 2: 1. The patient did not report any cardiovascular risk factor. Therefore, we concluded that PDA was responsible for congestive heart failure in this patient. We performed percutaneous closure of PDA, which was able to reverse left ventricular dilation and dysfunction, improving the patient's symptoms, at 1 month as well as 4 months after the interventional procedure. Although this kind of device is frequently used in the paediatric population, adult patients may present different challenges in proper management, such as poor visualization, calcification and pulmonary hypertension. In the description of the case reported here, we show that a PDA can present as congestive heart failure in the elderly. Percutaneous closure can be very effective in ameliorating left ventricular performance as well as symptoms.

Acad Radiol. 2009 Jun; 16(6): 726-32Budoff MJ, Ahmadi N, Sarraf G, Gao Y, Chow D, Flores F, Mao SSRATIONALE AND OBJECTIVES: Left ventricular hypertrophy (LVH) is associated with an increased risk of cardiac death. The present study evaluates whether using computed tomographic (CT)-derived criteria for normal myocardial mass can improve detection of LVH on CT angiography (CTA). MATERIALS AND METHODS: A total of 2238 subjects (63 +/- 9 years, 27% female) who underwent CTA were studied. To identify normal limits for CT-derived myocardial mass, we studied normal subjects (those without diabetes, hypertension, congestive heart failure, or coronary artery disease). Left ventricular mass (LVM) was measured manually using two different workstations. The CT criteria of LVH was defined as LVM above the 97th percentile per gender and compared to echocardiographic criteria (110 g/m(2) in women; 124 g/m(2) in men), and specificity and sensitivity of both models to detect LVH were calculated. RESULTS: The LVM was higher in men than women in normal cohorts (75.5 +/- 14.0 vs. 63.1 +/- 12.8 g/m(2), P = .001 with electron beam CTA and 78.5 +/- 11.9 vs. 65.0 +/- 9.2 g/m(2), P = .001 with 64 multidetector [MD] CT, respectively). The coefficient of variation between electron beam CTA and 64 MDCT for measuring LVM was 3.1%. Comparing the new CTA/64 MDCT criteria of LVH (103.0 g/m(2) in men; 89.0 g/m(2) in women) to the previous echocardiographic criteria of LVH, the specificity in women and men decreased from 100% in both genders by echocardiography to 91.8% and 92.6%, respectively, but the sensitivity increased from 42.0% to 100% and from 41.1% to 100%. CONCLUSION: This study suggests that CT-measured LVM has low variability and normal values based on CT criteria will potentially increase the early detection of LVH.