Reverse electrophysiologic remodeling after cardiac mechanical unloading for end-stage nonischemic cardiomyopathy.

BACKGROUND: Left ventricular assist devices (LVAD)-induced unloading appear to cause reverse cardiac remodeling. However, its effect on arrhythmogenicity is a controversial issue, and prospective data are lacking. We sought to investigate the impact of LVAD-induced unloading on the electrical properties of the failing heart. METHODS: We prospectively studied the effects of LVAD therapy on QRS, QT, and QTc durations and ventricular arrhythmias from electrocardiograms and 24-hour ambulatory electrocardiograms recorded before and during 6 months of mechanical support in 12 LVAD patients and 7 other patients with advanced nonischemic cardiomyopathy untreated with LVAD. RESULTS: After 1 week of LVAD support, QTc duration had decreased from 479 ± 79 ms to 411 ± 57 ms (p = 0.037), and QRS duration from 150 ± 46 ms to 134 ± 32 ms (p = 0.029). At 6 months, QTc was found to be 372 ± 56 ms (p = 0.046 versus baseline, 15% shortening) and QRS 118 ± 25 ms (p = 0.028 versus baseline, 11% shortening). A strong correlation was found between QTc shortening and increase in left ventricular ejection fraction and decrease in left ventricular filling pressures. After 2 months of LVAD support, premature ventricular contractions had decreased from 3,507 ± 4,252 to 483 ± 417 in 24 hours (p = 0.043), ventricular couplets from 82 ± 99 to 29 ± 25 in 24 hours (p = 0.05), and ventricular runs from 9 ± 8 to 10 ± 9 (not significant). No patient died suddenly or suffered a symptomatic arrhythmic event during follow-up. No significant electrocardiographic, functional, or hemodynamic change was observed in the 7 patients untreated with LVAD. CONCLUSIONS: The LVAD support caused progressive shortening of QTc and QRS intervals, consistent with reverse remodeling of the failing heart's electrical properties, accompanied by a decrease in frequency of ventricular arrhythmias.

Reversible Cortical Blindness as a Prominent Manifestation of Cerebral Embolism due to Infective Endocarditis.

Introduction. Infective endocarditis in the left heart may be complicated by stroke, due to embolisation from infectious valvular vegetations. Infarction of both occipital lobes, which are supplied by the posterior cerebral arteries, is infrequent, and is the cause of cortical blindness from lesion of the visual cortex. Cortical blindness is characterized by intact pupillary reflexes, a normal fundoscopy, and, rarely, denial of visual loss. Case Presentation. We report the case of a 58-year-old woman, recipient of a mechanical aortic valve, who presented with fever, multiple organ dysfunction, and cortical blindness. Transesophageal echocardiography and blood cultures confirmed the diagnosis of infective endocarditis caused by methicillin-sensitive Staphylococcus aureus. Computed tomography of the brain without contrast revealed the presence of infarctions in both occipital lobes. It is noteworthy that the visual loss resolved after treatment of endocarditis. Conclusions. A stroke occurring in a patient presenting with fever and a history of valvular heart disease strongly suggests the presence of infective endocarditis. Bilateral thromboembolic infarcts of the occipital lobes cause cortical blindness, that can resolve after treatment of endocarditis.

Increase in coronary blood flow by intra-aortic balloon counterpulsation in a porcine model of myocardial reperfusion.

BACKGROUND: Studies of the IABP have reported variable effects on coronary blood flow (CBF). The purpose of the present study was to measure the changes in coronary blood flow induced by intra-aortic balloon pump (IABP) counterpulsation in normal and reperfused porcine myocardium. METHODS: A 30-ml IABP was placed in the descending aorta of 6 open-chest pigs. Each pig underwent occlusion of the mid-left anterior descending (LAD) coronary artery for 1 h, followed by reperfusion for 2 h. The effects of IABP support on systolic aortic pressure (SAP) and aortic end-diastolic pressure were recorded. The mean CBF, distal to the LAD occlusion site was measured at baseline and during reperfusion, with and without IABP counterpulsation. RESULTS: The IABP decreased SAP and aortic end-diastolic pressure in normal and reperfused myocardium, and maintained a peak aortic diastolic augmentation at the level of SAP. In normal myocardium, the IABP decreased mean CBF by 8.4+/-2.2% (p<0.001). At 2, 15, 30, 60, 90 and 120 min of reperfusion, the IABP increased mean CBF by 11.5+/-6.8%, 8.0+/-7.0%, 11.2+/-6.9%, 12.4+/-12.9%, 23.5+/-9.9% and 8.9+/-6.9%, of the corresponding value without the assistance of the IABP (all p<0.05). CONCLUSIONS: In the normal heart, IABP counterpulsation decreased CBF, probably because of a decrease in myocardial oxygen demand from a decreased afterload. During reperfusion the IABP increased CBF, suggesting that it might effectively mitigate the no-reflow phenomenon.

Amiodarone attenuates the proarrhythmic effects of dobutamine in patients with advanced congestive heart failure.

INTRODUCTION: The long-term use of positive inotropic pharmaceuticals in patients suffering from end-stage congestive heart failure (CHF) has been associated with increased mortality, presumed to be due to proarrhythmia. Oral amiodarone combined with intermittent dobutamine infusions (IDI), on the other hand, has been shown to increase survival. This study evaluated the effects of oral amiodarone on the arrhythmias caused by dobutamine in patients with advanced CHF. METHODS: Thirty patients with CHF, in New York Heart Association functional class III or IV despite optimal medical therapy, were treated with weekly 8-h infusions of dobutamine 10 Ig/kg/min. All patients were treated for 1 month with oral amiodarone, 400 mg/day, before initiation of IDI. A 24-h ambulatory electrocardiogram was recorded on the day before dobutamine infusion and repeated the next day, starting with the onset of infusion. RESULTS: The average heart rate on the 24-h ambulatory electrocardiogram was 72 +/- 14 beats/min before vs. 72 +/- 12 beats/min during IDI (p=1.000). Likewise, dobutamine did not increase the frequency of premature ventricular complexes (23 +/- 32 per h before vs. 42 +/- 69 per h during infusion, p=0.131), ventricular couplets (18 +/- 36 per 24 h vs. 17 +/- 28 per 24 h, p=0.859), or the incidence of non-sustained ventricular tachycardia (27% vs. 40%, p=0.383). No patient developed ventricular fibrillation or sustained ventricular tachycardia during or after IDI. CONCLUSIONS: Chronic low-dose oral amiodarone attenuates the proarrhythmic effects of dobutamine, increasing the safety of ambulatory IDI.

Long-term survival and outcomes after hospitalization for acute myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Cardiogenic shock is the leading cause of death during hospitalization for acute myocardial infarction (MI). However, little data exist regarding the long-term outcomes of patients who survived the acute phase of MI and were discharged from the hospital. METHODS: We retrospectively reviewed the records of 81 consecutive patients referred for management of acute MI and cardiogenic shock to analyze their in-hospital and long-term outcomes. RESULTS: Mean systemic systolic and central venous pressures at presentation were 74 +/- 15 and 17 +/- 7 mm Hg, respectively. Intra-aortic balloon counterpulsation (IABC) was implemented in all patients for a mean of 88 +/- 83 hours. Thrombolytics were administered in 49% and mechanical ventilation applied in 46% of patients. Primary angioplasty could not be performed in any patient, while 17 patients later underwent myocardial revascularization during hospitalization. There were 37 in-hospital survivors (45.7%). The 1-year survival after discharge from the hospital was 87.6% in the overall population, versus 100% among patients who underwent in-hospital myocardial revascularization, versus 78.9% among nonrevascularized patients (p = 0.079). Over a mean follow-up of 85 +/- 47 mo, survival after discharge from the index hospitalization was 44.9% in the overall population, versus 56.2% among revascularized patients, versus 36.4% among nonrevascularized patients (p = 0.277). Heart failure developed in 51.6% of patients who were discharged from the hospital. CONCLUSIONS: In this single center analysis, the long-term survival after acute MI complicated by cardiogenic shock was high with nearly 50% of patients surviving free from heart failure.

Anemia in chronic heart failure.

Anemia is frequently observed in patients with chronic heart failure and is increasingly recognized as an important and treatable condition. The present review will summarize the current knowledge of the prevalence, causative factors, and pathophysiologic correlates of anemia in chronic heart failure. Despite increasing knowledge of anemia there are very few evidence-based recommendations for treatment. Potential benefits of therapy with supplemental hematinics such as iron, subcutaneous erythropoiesis-stimulating agents, or both will also be discussed.

Hemodynamic effects of levosimendan in acute myocardial infarction complicated by cardiogenic shock and high systemic vascular resistance.

BACKGROUND: Levosimendan (LEVO), a new inodilator, improves hemodynamic function in patients with decompensated heart failure and preserved arterial blood pressure. Data on its use in patients with cardiogenic shock (CS) are scarce. The present study was undertaken to evaluate the hemodynamic effects of supplemental therapy with levosimendan (LEVO) in acute myocardial infarction (MI) and refractory cardiogenic shock (CS). METHODS: In 25 patients presenting in CS after acute MI, LEVO was administered for 24 h in doses ranging between 0.05 and 0.20 microg/kg/min, as tolerated, preceded by 6-microg/kg over 10 min, in addition to catecholamines. Hemodynamic measurements were made before and 24 h after initiation of the LEVO infusion. RESULTS: Hemodynamic improvement was limited to 13 patients with systemic vascular resistances (SVR) > or =18 W. LEVO increased the cardiac index from 1.5+/-0.3 l/min/m2 to 2.1+/-0.4 l/min/m2 (P = 0.002) and cardiac power from 0.462+/-0.164 W to 0.645+/-0.179 W (P = 0.022), and decreased SVR from 23+/-5 to 21+/-6.7 Wood units (P = 0.001) and pulmonary capillary wedge pressure from 24+/-9 mmHg to 16+/-11 mmHg (P = 0.059). No hemodynamic improvement was observed during LEVO administration in 12 patients with SVR < 18 W. CONCLUSION: The hemodynamic benefit conferred by LEVO added to catecholamines in patients with CS after acute MI was limited to patients with high SVR.

Intra-aortic balloon counterpulsation for the treatment of myocardial infarction complicated by acute severe heart failure.

Intractable heart failure (HF) remains a leading fatal complication of acute myocardial infarction (AMI). Intra-aortic balloon pump (IABP) counterpulsation assists the failing left ventricle and accelerates the functional recovery of stunned myocardium. Despite its remarkable performance, the beneficial effects of the IABP in the setting of acute HF or cardiogenic shock complicating AMI have not been confirmed in a randomized clinical trial. Instead, large amounts of information have been collected in observational studies or in retrospective analyses of randomized trials of reperfusion strategies in patients with AMI. The strategy of "stabilize with IABP, treat with reperfusion, and transfer for complete revascularization" has, thus far, yielded the best outcomes, and every effort should be made to implement this strategy in all patients presenting with AMI and severe HF.

Stauffer's syndrome as a prominent manifestation of renal cancer: a case report.

BACKGROUND: Renal cell carcinoma is associated with a wide spectrum of para-neoplastic syndromes, which may be precursors of primary or recurrent disease. Non-metastatic hepatic dysfunction in patients suffering from renal cell carcinoma is known as Stauffer's syndrome. It is associated with the production of cytokines by the tumour, and several biochemical abnormalities, including elevated serum alkaline phosphatase. CASE PRESENTATION: We describe a 36-year-old woman presenting with various non-specific, systemic disease manifestations, and elevated liver enzymes due to cholestasis as the main laboratory abnormality. Imaging studies showed a solid mass in the left kidney, which, after surgical excision, was identified as renal cell carcinoma. No metastasis was found. CONCLUSION: Stauffer syndrome may precede other manifestations of renal cell carcinoma. In case of unexplained abnormal liver function, particularly in presence of systemic symptoms, underlying renal cell carcinoma should be excluded by focused investigations.

Intra-aortic balloon counterpulsation and delayed revascularization for myocardial infarction and shock in the absence of primary angioplasty: a treatment strategy with or without thrombolysis?

OBJECTIVE: When revascularization facilities are not available, thrombolytic therapy (TT) added to intra-aortic balloon counterpulsation (IABC) has been proposed as initial therapy for the management of patients presenting with postmyocardial infarction (MI) cardiogenic shock, followed by prompt transfer to another institution for revascularization. The use of TT in this setting, however, remains controversial. METHODS: We reviewed the records of 81 consecutive patients admitted with cardiogenic shock after acute MI and compared the outcomes of patients initially stabilized, including IABC as an adjunct to TT (IABC+TT group, n=40), with those patients initially stabilized with IABC and no TT (IABC group, n=41). RESULTS: The baseline characteristics of the two study groups were similar. The in-hospital and 6-month survival rates were 47.5 and 33.3% in the IABC+TT group versus 43.9 and 31.6% in the IABC group, respectively (NS). Except for mechanical ventilation more frequently required in the IABC group, other outcome measures were similar in both groups. The in-hospital (76.5 vs. 36.5%, P=0.008) and 6-month (60 vs. 25.4%, P=0.01) survival rates were significantly higher in patients who underwent delayed invasive revascularization, than in patients who underwent no invasive revascularization attempt. CONCLUSION: In patients presenting with acute MI and cardiogenic shock, TT as an adjunct to IABC added no therapeutic benefit when compared with IABC alone. In contrast, the survival of patients was significantly increased by delayed invasive revascularization in both treatment groups. These observations suggest that, when revascularization facilities are not available, stabilization with IABC, followed by prompt transfer for delayed revascularization to a tertiary care hospital, might be the preferred management strategy for patients presenting with post-MI cardiogenic shock.

Wegener's granulomatosis presenting as a renal mass.

Wegener's granulomatosis is a systemic necrotizing vasculitis that usually involves the kidneys, typically causing segmental necrotizing glomerulonephritis. An association between Wegener's granulomatosis and renal cell carcinoma was recently reported. We describe a case of Wegener's granulomatosis presenting as a renal mass in a 72-year-old woman. Histologic examination of the mass revealed granulomatous inflammation, an extremely rare manifestation of this disease. We also review the incidence of renal mass in Wegener's granulomatosis and highlight the importance of excluding the coexistence of renal cell carcinoma.

Reverse remodeling during long-term mechanical unloading of the left ventricle.

A significant proportion of patients placed on long-term mechanical circulatory support for end-stage heart failure can be weaned from mechanical assistance after functional recovery of their native heart ("bridge to recovery"). The pathophysiological mechanisms implicated in reverse remodeling that cause a sustained functional myocardial recovery have recently become the subject of intensive research, expected to provide information with a view to accurately identify reliable prognostic indicators of recovery. In addition, this kind of information will enable changes in the strategy of myocardial recovery by modifying the duration and scale of the unloading regimen or by combining it with other treatments that promote reverse remodeling.

Possible everolimus-induced, severe, reversible encephalopathy after cardiac transplantation.

Neurotoxicity is a common adverse effect of cyclosporine (CsA) in transplant recipients. Although most patients develop mild toxic manifestations, leukoencephalopathy with seizures, visual complications, psychiatric symptoms and motor and speech disorders may occur. Whether everolimus exacerbates the neurotoxicity of CsA is not known. We describe a patient who developed severe neurologic complications, consistent with CsA-induced neurotoxicity, developing 7.5 years after cardiac transplantation, 3 months after everolimus was added to the immunosuppressive regimen.

Immune status evaluation of patients with chronic heart failure.

Chronic heart failure (CHF) may be considered a state of immune activation and persistent inflammation expressed by increased circulating levels of pro- and anti-inflammatory cytokines. The purpose of the study was to investigate the immune status in patients with CHF compared to normal individuals. We measured serum cytokine levels as well as cytokine production after ex vivo LPS stimulation of whole blood taken from 14 patients with CHF and 14 healthy volunteers. We used 500 pg/ml of LPS for an incubation period of 4h to stimulate 100 microL of whole blood. Patients with CHF had significantly higher levels of TNF-RI, and TNF-RII in serum compared to normal individuals. TNF-alpha, IL-6, and IL-10 did not differ significantly. After LPS stimulation, patients with CHF had significantly higher levels of TNF-alpha and IL-10, and significantly lower IL-6 levels compared to normal individuals. TNF-alpha receptors did not differ significantly. Patients with CHF may be found in a pro- as well as an anti-inflammatory state. They also do not develop endotoxin tolerance in an ex vivo laboratory model using whole blood stimulated with LPS. They may have increased TNF-alpha and IL-10 production after LPS stimulation of whole blood, which may contribute to a worsening of heart function, more severe disease presentation and a worse outcome during infections.

Etiology of anemia in patients with advanced heart failure.

OBJECTIVES: We prospectively investigated the causes of anemia in patients with advanced congestive heart failure (CHF). BACKGROUND: Anemia is common in patients with advanced CHF, and its etiology is generally considered to be multifactorial. However, despite its importance, precise information is lacking regarding the prevalence of putative etiologic factors. METHODS: Patients who were hospitalized for decompensated advanced CHF and who were stabilized after their initial treatment underwent evaluation of "clinically significant" anemia, defined as a hemoglobin content <12 g/dl for men and <11.5 g/dl for women. Patients with a serum creatinine concentration >3 mg/dl or patients with concurrent diseases that are known to cause anemia were not included. The initial evaluation included measurements of vitamin B(12), folic acid, thyroid-stimulating hormone, erythropoietin, lactate dehydrogenase, Coombs test, multiple fecal occult tests, and bone marrow aspiration. Patients without diagnosis by these methods underwent red cell mass measurement with (51)Cr assay. RESULTS: The mean age of the 37 patients was 57.9 +/- 10.9 years and mean left ventricular ejection fraction 22.5 +/- 5.9%. Iron deficiency anemia was confirmed by bone marrow aspiration in 27 patients (73%), 2 patients (5.4%) had dilutional anemia, and 1 patient (2.7%) had drug-induced anemia. No specific cause was identified in 7 patients (18.9%) who were considered to have "anemia of chronic disease." Serum ferritin for the iron-deficient patients was not a reliable marker of iron deficiency in this population. CONCLUSIONS: In this group of patients, iron deficiency was the most common cause of anemia. The iron status of patients with end-stage chronic CHF should be thoroughly evaluated and corrected before considering other therapeutic interventions.

Cardiogenic shock due to isolated right ventricular infarction in an elderly woman.

A 78-year-old hypertensive woman with no prior history of ischemic heart disease arrived at the hospital complaining of weakness and profound fatigue. Four days earlier, she had experienced substernal chest pain associated with nausea and vomiting. A standard 12-lead electrocardiogram showed marked ST-segment elevation and negative T waves in leads V1 and V2. The patient was treated with anti-thrombotic therapy, dobutamine and dopamine infusions. Angiography showed proximal occlusion of a small, non-dominant right coronary artery and no clinically significant disease in the left coronary artery. Isolated right ventricular infarction accounted for the cardiogenic shock in this elderly patient. She received conservative medical treatment and was discharged in good condition.

Prevalence and prognostic significance of anemia in patients with congestive heart failure treated with standard vs high doses of enalapril.

BACKGROUND: Anemia is common in patients with congestive heart failure (CHF), although its etiology and pathophysiology remain largely unexplained. The purpose of this study was to examine the prognostic significance of a low hematocrit (Hct) in patients with CHF and the possible role of angiotensin-converting enzyme inhibition in anemia development. METHODS: Hct was measured at the time of enrollment of 160 patients with CHF, mean age 56 +/- 12 years, in New York Heart Association (NYHA) functional class 2.6 +/- 0.7 and with left ventricular ejection fraction of 20 +/- 9%. They were randomized to standard (mean: 17.9 +/- 4.3 mg/day) or high (mean: 42 +/- 19.3 mg/day) doses of enalapril. The follow-up duration was 2 years. Cox regression models were used to identify prognostic factors, and correlations among individual variables were tested. RESULTS: Mean baseline Hct was 42.7 +/- 5%. In multivariate analyses, low Hct (p = 0.036), older age (p = 0.022) and low systolic blood pressure (p = 0.032) were independent predictors of death within 2 years. A correlation was found between baseline Hct and NYHA class (Spearman's correlation coefficient: -0.183, p = 0.008). A significant decrease in Hct from 43.2 +/- 4.9% at baseline to 40.7 +/- 4.4% at 2 years was observed in the group treated with high doses of enalapril (p < 0.001). CONCLUSIONS: Low baseline Hct predicted poor 2-year prognosis in patients with CHF. Enalapril administered in high doses increased the incidence of anemia in this population. The underlying pathophysiologic mechanism and effects of maintaining a normal Hct on clinical outcomes remain to be determined.

The long-term survival benefit conferred by intermittent dobutamine infusions and oral amiodarone is greater in patients with idiopathic dilated cardiomyopathy than with ischemic heart disease.

BACKGROUND: Intermittent dobutamine infusions (IDI) combined with oral amiodarone improve the survival of patients with end-stage congestive heart failure (CHF). The purpose of the present study was to evaluate whether the response to long-term treatment with IDI+amiodarone is different in patients with ischemic heart disease (IHD) versus idiopathic dilated cardiomyopathy (IDC). METHODS: The prospective study population consisted of 21 patients with IHD (the IHD Group) and 16 patients with IDC (the IDC Group) who presented with decompensated CHF despite optimal medical therapy, and were successfully weaned from an initial 72-h infusion of dobutamine. They were placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 microg/kg/min, for 8 h. RESULTS: There were no differences in baseline clinical and hemodynamic characteristics between the 2 groups. The probability of 2-year survival was 44% in the IDC Group versus 5% in the IHD Group (long-rank, P=0.004). Patients with IDC had a 77% relative risk reduction in death from all causes compared to patients with IHD (odd ratio 0.27, 95% confidence interval 0.13 to 0.70, P=0.007). In contrast, no underlying disease-related difference in outcomes was observed in a retrospectively analyzed historical Comparison Group of 29 patients with end stage CHF treated by standard methods. CONCLUSIONS: Patients with end stage CHF due to IDC derived a greater survival benefit from IDI and oral amiodarone than patients with IHD.