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Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure

BACKGROUND The benefit of an implantable cardioverter-defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT). METHODS In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, ≤35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death. RESULTS After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval [CI], 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29). CONCLUSIONS In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH ClinicalTrials.gov number, NCT00542945 .).

Incidence of ventricular arrhythmias in patients on long-term support with a continuous-flow assist device (HeartMate II).

The incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients supported with a continuous-flow left ventricular assist device (LVAD) has not been investigated in detail. In 23 consecutive recipients of a HeartMate II, we analyzed the incidence of VT/VF during a total of 266 months of follow-up. Sustained VT or VF occurred in 52% of the patients, with the majority of arrhythmias occurring in the first 4 weeks after LVAD implantation. VT/VF requiring implantable cardioverter-defibrillator (ICD) shock or external defibrillation occurred in 8 patients and significant hemodynamic instability ensued in 3 patients. There were no clear predictors of VT/VF, and it is argued that prophylactic ICD implantation should be considered in patients supported with a continuous-flow LVAD.

Prevalence, predictors, and survival in pulmonary hypertension related to end-stage chronic obstructive pulmonary disease

BACKGROUND The prevalence, prognostic importance, and factors that predict the presence and degree of pulmonary hypertension (PH) diagnosed with right heart catheterization (RHC) in patients with end-stage chronic obstructive pulmonary disease (COPD) remain unclear. METHODS This retrospective study included 409 patients (61% women) with COPD/emphysema or α-1-antitrypsin deficiency who underwent lung transplant evaluation during 1991 to 2010. We analyzed the occurrence and degree of PH and compared demographics, oxygenation, lung function, hemodynamics, functional capacity, and survival in patients with and without PH. Prediction of PH was assessed using univariate and multivariate regression analysis. RESULTS The mean age at evaluation was 54 ± 7 years. All patients were in New York Heart Association functional class III-IV, with forced expiratory volume in 1 second of 23% ± 7% and total lung capacity of 126% ± 21% of predicted. PH was present in 146 (36%). The analysis excluded 53 (13%) with pulmonary venous hypertension (PVH). The distribution of the mean pulmonary artery pressure (mPAP) in patients with or without PH showed a unimodal normally distributed population, with a mean of 23.8 ± 6.0 mm Hg. Predictors of PH were partial pressures of oxygen and carbon dioxide. The 5-year survival rate was 37% in COPD patients with PH vs 63% in patients without PH (p = 0.016). Survival after lung transplantation did not differ (p = 0.37). CONCLUSIONS RHC verified PH in 36% of COPD patients. Hypoxemia and hypercapnia were associated with mPAP. PH is associated with worse survival in COPD, but PH does not influence the prognosis after lung transplantation.

Apelin : A new plasma marker of cardiopulmonary disease

OBJECTIVES Dyspnea is a major symptom of both parenchymal lung disease and chronic heart failure. Underlying cardiac dysfunction can be assessed by measurement of cardiac-derived B-type natriuretic peptide or its precursor in plasma. However, no specific endocrine marker of the lung parenchyma has so far been identified. We therefore examined whether plasma concentrations of apelin, a novel inotropic hormone, is affected in patients with chronic parenchymal lung disease without cardiac dysfunction. METHODS AND RESULTS Patients with severe chronic parenchymal lung disease and normal cardiac function (n=53), idiopathic pulmonary hypertension with increased right ventricular pressure (n=10), and patients with severe left ventricular systolic dysfunction (n=22) were enrolled. Plasma apelin-36 and proBNP concentrations were measured with radioimmunoassays. While proBNP plasma concentrations were unaffected in chronic parenchymal lung disease patients compared to normal subjects, the apelin-36 concentration was reduced 3.3-fold (median 35 pmol/l (0-162 pmol/l) vs. 117 pmol/l (55-232 pmol/l), P<0.001). Moreover, the apelin-36 concentration was decreased in chronic heart failure patients (2.1-fold, P<0.01) and in patients with idiopathic pulmonary hypertension (4.0-fold, P<0.001). In contrast, the proBNP concentration was highly increased in both chronic heart failure and idiopathic pulmonary hypertension patients. CONCLUSION Plasma concentrations of apelin-36, a novel inotropic peptide, are decreased in patients with chronic parenchymal lung disease and preserved cardiac function. Combined measurement of apelin-36 and proBNP may be a new diagnostic approach in distinguishing pulmonary from cardiovascular causes of dyspnea.

Pulmonary Hypertension in End-stage Pulmonary Sarcoidosis: Therapeutic Effect of Sildenafil?

BACKGROUND The objectives of this study were to assess the frequency and severity of pulmonary hypertension (PH) and the effect of sildenafil treatment in patients with recalcitrant pulmonary sarcoidosis. METHODS This investigation was a single-center, retrospective study of all patients (n = 25) with end-stage pulmonary sarcoidosis referred for lung transplantation. Hemodynamic measurements were evaluated by right-side cardiac catheterization in 24 of 25 patients. Sildenafil treatment for patients with sarcoidosis-associated PH was introduced in April 2004. RESULTS The study group of 24 patients (16 men, 8 women) had a median age of 45 (range 35 to 58) years, and duration of sarcoidosis of 11 (range 2 to 38) years. Mean pulmonary arterial pressure (MPAP) was median 36 (range 18 to 73) mm Hg. PH (MPAP >25 mm Hg) was present in 19 of 24 patients (79%). Sildenafil was administered to 12 of 13 patients at a dose of 150 (range 75 to 225) mg/day for 4 (range 1 to 12) months. Sildenafil treatment was associated with reductions in MPAP of -8 mm Hg (CI -1 to -15 mm Hg), and PVR -4.9 Wood units (CI -7.2 to -2.6 Wood units). Cardiac output and cardiac index also increased during treatment (p = 0.01, respectively). There were no consistent changes in 6-minute walk distance. CONCLUSIONS Patients with severe pulmonary sarcoidosis have a high prevalence of PH. Sildenafil treatment was associated with significant improvements in hemodynamic parameters.

B-type natriuretic peptide and its precursor in cardiac venous blood from failing hearts.

Plasma concentrations of B‐type natriuretic peptide (BNP‐32) and its precursor (proBNP) are increased in chronic heart failure. Accordingly, BNP‐32 and proBNP are both being implemented as clinical markers.

Underestimation of plasma volume changes in humans by hematocrit/hemoglobin method

During water immersion in humans, the use of changes in hematocrit (Hct) and hemoglobin concentration (Hb) underestimates the relative changes in plasma volume (PV) as measured directly with Evans blue (EB). It is not known whether the same is the case during posture changes. Therefore, changes in PV were determined with an EB dilution technique in 10 males before, during, and after an acute posture change from seated to 6 degrees head-down tilt (HDT). The EB method was improved to take into account changes in transcapillary escape rate of albumin-bound EB. Furthermore, blood was sampled from a central venous catheter. Hct and Hb were simultaneously measured. During HDT, PV determined with EB increased by 9.3 +/- 2.0% but increased only 4.5 +/- 0.9% when calculated with the Hct/Hb method (P < 0.05 vs. EB measurements). Thus use of the Hct/Hb method in humans leads to underestimation of the change in PV by as much as 50% during an acute change in posture. Therefore, a direct tracer-dilution method must be used for accurate estimations of changes in PV during changes in posture or other antiorthostatic maneuvers.During water immersion in humans, the use of changes in hematocrit (Hct) and hemoglobin concentration (Hb) underestimates the relative changes in plasma volume (PV) as measured directly with Evans blue (EB). It is not known whether the same is the case during posture changes. Therefore, changes in PV were determined with an EB dilution technique in 10 males before, during, and after an acute posture change from seated to 6° head-down tilt (HDT). The EB method was improved to take into account changes in transcapillary escape rate of albumin-bound EB. Furthermore, blood was sampled from a central venous catheter. Hct and Hb were simultaneously measured. During HDT, PV determined with EB increased by 9.3 ± 2.0% but increased only 4.5 ± 0.9% when calculated with the Hct/Hb method ( P < 0.05 vs. EB measurements). Thus use of the Hct/Hb method in humans leads to underestimation of the change in PV by as much as 50% during an acute change in posture. Therefore, a direct tracer-dilution method must be used for accurate estimations of changes in PV during changes in posture or other antiorthostatic maneuvers.

Pro-brain natriuretic peptide as marker of cardiovascular or pulmonary causes of dyspnea in patients with terminal parenchymal lung disease

BACKGROUND Increased plasma concentrations of pro-atrial natriuretic peptide (proANP) and pro-brain natriuretic peptide (proBNP) are features of left ventricular impairment. However, concentrations of proANP and proBNP in patients with isolated terminal parenchymal lung disease are not known. Therefore, we measured the plasma concentrations of natriuretic precursor peptides in patients with terminal parenchymal lung disease who had normal left ventricular function and who were referred for evaluation for lung transplantation. METHODS We measured plasma N-terminal proANP and proBNP in patients undergoing right heart catheterization (n = 50) and related results to hemodynamic variables obtained during catheterization. RESULTS Plasma proBNP concentrations were unaffected in patients with terminal parenchymal lung disease and normal left ventricular function (median, 2.5 pmol/liter; range, 0-22; upper reference limit, 15 pmol/liter). In contrast, patients with primary pulmonary hypertension displayed more than a 40-fold increase in plasma proBNP concentrations (median, 107 pmol/liter vs 2.5 pmol/liter, p < 0.0001). Plasma N-terminal proANP increased moderately (median, 664 pmol/liter; range, 36-1620; upper reference limit, 600 pmol/liter) but correlated to plasma proBNP concentrations (r = 0.47, p < 0.0001). Finally, regional vascular proBNP concentrations revealed the heart as the secretory site. CONCLUSIONS Our findings strongly support the contention that natriuretic peptide measurements are efficient markers for cardiovascular causes of dyspnea. Moreover, our results eliminate natriuretic peptides as markers of moderate pulmonary hypertension in patients with terminal parenchymal lung disease.

Nationwide fluoroscopic screening of recalled riata defibrillator leads in Denmark

BACKGROUND The natural history of insulation defects with inside-out conductor externalization in recalled St Jude Medical Riata defibrillator leads is not well understood. OBJECTIVES To determine the prevalence of externalization in a nationwide screening. Secondary aims were to examine time dependence and location of externalization, association with electrical failure, and fluoroscopic diagnostic performance. METHODS All 299 patients with recalled Riata leads in Denmark were identified, and all except one underwent fluoroscopy and device interrogation. Externalizations were confirmed by multiple investigators. RESULTS The prevalence of externalization was 32 of 298 (11%) at a mean dwell time of 5.1 years. The prevalence was 21 of 98 (21%) for 8-F leads and 11 of 200 (6%) for 7-F leads; however, 8-F leads had longer dwell times. The degree of externalization was correlated with dwell time (Spearmans ρ = .37; P = .03). Externalization more often included the lead segment below the tricuspid annulus in dual coil leads than in single coil leads (69% vs 16%; P = .004). No association was observed between externalization and electrical function. Fluoroscopic diagnostic performance was good with positive and negative predictive values of 88% and 99%, respectively. CONCLUSIONS The prevalence of externalization in a nationwide screening is at the same level as reported in previous studies with similar lead dwell times. The degree of externalization is time dependent, and location seems to differ between single and dual coil leads. Long-term lead performance and association with electrical failure need further clarification. Fluoroscopy has a good diagnostic performance in clinical practice.

Age and Outcomes of Primary Prevention Implantable Cardioverter-Defibrillators in Patients With Nonischemic Systolic Heart Failure

Background: The DANISH study (Danish Study to Assess the Efficacy of ICDs [Implantable Cardioverter Defibrillators] in Patients With Non-Ischemic Systolic Heart Failure on Mortality) did not demonstrate an overall effect on all-cause mortality with ICD implantation. However, the prespecified subgroup analysis suggested a possible age-dependent association between ICD implantation and mortality with survival benefit seen only in the youngest patients. The nature of this relationship between age and outcome of a primary prevention ICD in patients with nonischemic systolic heart failure warrants further investigation. Methods: All 1116 patients from the DANISH study were included in this prespecified subgroup analysis. We assessed the relationship between ICD implantation and mortality by age, and an optimal age cutoff was estimated nonparametrically with selection impact curves. Modes of death were divided into sudden cardiac death and nonsudden death and compared between patients younger and older than this age cutoff with the use of &khgr;2 analysis. Results: Median age of the study population was 63 years (range, 21–84 years). There was a linearly decreasing relationship between ICD and mortality with age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.003–1.06; P=0.03). An optimal age cutoff for ICD implantation was present at ⩽70 years. There was an association between reduced all-cause mortality and ICD in patients ⩽70 years of age (HR, 0.70; 95% CI, 0.51–0.96; P=0.03) but not in patients >70 years of age (HR, 1.05; 95% CI, 0.68–1.62; P=0.84). For patients ⩽70 years old, the sudden cardiac death rate was 1.8 (95% CI, 1.3–2.5) and nonsudden death rate was 2.7 (95% CI, 2.1–3.5) events per 100 patient-years, whereas for patients >70 years old, the sudden cardiac death rate was 1.6 (95% CI, 0.8–3.2) and nonsudden death rate was 5.4 (95% CI, 3.7–7.8) events per 100 patient-years. This difference in modes of death between the 2 age groups was statistically significant (P=0.01). Conclusions: In patients with systolic heart failure not caused by ischemic heart disease, the association between the ICD and survival decreased linearly with increasing age. In this study population, an age cutoff for ICD implantation at ⩽70 years yielded the highest survival for the population as a whole. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945.