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 .).

The impact of implantable cardioverter-defibrillator implantation on health-related quality of life in the DANISH trial.

AIM: The Danish Study to Assess the Efficacy of Implantable Cardioverter-Defibrillators (ICD) in Patients with Non-ischaemic Systolic Heart Failure (HF) on Mortality (DANISH) found no overall effect on all-cause mortality. The effect of ICD implantation on health-related quality of life (HRQoL) remains to be established as previous trials have demonstrated conflicting results. We investigated the impact of ICD implantation on HRQoL in patients with non-ischaemic systolic HF, a prespecified secondary endpoint in DANISH. METHODS AND RESULTS: In DANISH, a total of 1116 patients with non-ischaemic systolic HF were randomly assigned (1:1) to ICD implantation or usual clinical care (control). Patients completed disease-specific HRQoL as assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ; 0-105, high indicating worse). Changes in HRQoL 8 months after randomization were assessed with a mixed-effects model. At randomization, MLHFQ was completed by 935 (84%) patients (n = 472 in the ICD group and n = 463 in the control group) and was reassessed in 274 (58%) and 292 (63%) patients, respectively after 8 months for the primary analysis. Patients in the ICD group vs. the control group had similar improvements in MLHFQ after 8 months [least square mean -7.0 vs. -4.2 (P = 0.13)]. A clinically relevant improvement (decrease ≥5) in the MLHFQ overall score at 8 months was observed in 151 patients in the ICD group and 148 patients in the control group [55% vs. 51%, respectively (P = 0.25)]. CONCLUSION: Implantable cardioverter-defibrillator implantation in patients with non-ischaemic systolic HF did not significantly alter HRQoL compared with patients randomized to usual clinical care.

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 χ2 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.

Study Design and Cohort Description of DEFIB-WOMEN: A National Danish Study in Patients with an ICD.

BACKGROUND: Little systematic evidence is available on potential gender differences in patients with an implantable cardioverter defibrillator (ICD) from a real-world cohort. We designed the DEFIB-WOMEN (The Utilization of Implantable Cardioverter DEFIBrillator Therapy in the Treatment of Heart Disease: Clinical and Psychological outcomes in WOMEN) study to examine gender differences on (1) patient-reported outcomes (PROs), (2) procedure- and device-related complications, and (3) ventricular tachyarrhythmia and mortality. This presents the study design and baseline characteristics of the cohort. METHODS: DEFIB-WOMEN is a national, multicenter, prospective, observational study. First-time implanted patients are asked to complete PROs at several time points. Information on baseline and follow-up characteristics are captured from patients' medical records, purpose-designed questions, and the Danish national registers. The DEFIB-WOMEN cohort is composed of 1,790 (19% women; 343/1,790) patients implanted between June 2010 and April 2013. RESULTS: Women and men differed on several demographic and clinical baseline characteristics, including on the prescription of ß-blockers, statins, angiotensin-converting enzyme inhibitors, and psychotropic agents. Although women generally had a healthier clinical profile, they reported significantly more symptoms of anxiety and depression and ICD concerns (fear of shock) as compared to men. These differences were not only statistically significant but also clinically relevant, with the magnitude of the differences in anxiety and ICD concerns being 0.44 and 0.42, respectively, as indicated by Cohen's effect size index. CONCLUSIONS: These preliminary results indicate that women with an ICD experience particularly more anxiety and ICD concerns as compared to men at the time of implant. Future results of DEFIB-WOMEN will show whether these gender differences persist and whether there are also gender differences in complications and survival.

CIED infection with either pocket or systemic infection presentation--complete device removal and long-term antibiotic treatment; long-term outcome.

OBJECTIVE: Cardiovascular implantable electronic device (CIED) infections are increasing in numbers. The objective was to review the clinical presentation and outcome in patients affected with CIED infections with either local pocket or systemic presentation. DESIGN: All device removals due to CIED infection during the period from 2005 to 2012 were retrospectively reviewed. CIED infections were categorized as systemic or pocket infections. Treatment included complete removal of the device, followed by antibiotic treatment of six weeks. RESULTS: Seventy-one device removals due to infection (32 systemic and 39 pocket infections) were recorded during the study period. Median follow-up time was 26 (IQR 9-41) months, 30 day and 12 month mortality were 4% and 14%, respectively. There was no long-term difference in mortality between patients with pocket vs. systemic infection (p = 0.48). During follow-up no relapses and two cases of new infections were noted (2.8%). CONCLUSIONS: CIED infection with systemic or pocket infection was difficult to distinguish in clinical presentation and outcome. Complete device removal and antibiotic treatment of long duration was safe and without relapses.

Mortality and appropriate and inappropriate therapy in patients with ischaemic heart disease and implanted cardioverter-defibrillators for primary prevention: data from the Danish ICD Register.

AIMS: To evaluate the incidences of and risk factors predisposing to appropriate and inappropriate shocks and mortality in a 'real-world' population of patients with ischaemic heart disease (IHD) and implantable cardioverter defibrillators (ICD) for primary prevention of sudden cardiac death (SCD). METHODS AND RESULTS: In this nationwide cohort, we prospectively followed 1609 patients with IHD and left ventricular dysfunction from the Danish ICD Register who received an ICD for primary prevention of SCD (1 January 2007 to 30 November 2011). Primary study outcomes were appropriate shocks, inappropriate shocks, and all-cause mortality. Secondary study outcomes included the composite endpoints: appropriate therapy and inappropriate therapy (defined as shock or anti-tachycardia pacing). All-cause mortality was 12.1% during a mean follow-up time of 1.9 ± 1.3 years. Inappropriate shocks and therapy occurred in 2.6% and 3.7% during follow-up, respectively. Appropriate shocks and therapy was identified in 7.8% and 13.4%, respectively. Time-dependent multivariable Cox regression analyses were used to identify risk factors of inappropriate/appropriate shock, therapy and mortality. Implantation of a dual-chamber ICD was associated with increased risk of both inappropriate shocks and any inappropriate therapy compared to single-chamber ICD [hazard ratios (HR) = 2.45; confidence intervals (CI):1.16-5.14 and HR = 2.38; CI:1.28-4.42, respectively]. No excess risk of mortality was associated with any device type. CONCLUSION: In this nationwide study of IHD patients with an ICD for primary prevention of SCD, the incidence of appropriate shocks as well as inappropriate shocks were significantly lower than reported in randomized trials. Implantation of a dual-chamber ICD was associated with more inappropriate shocks compared with single chamber devices.

Attitudes towards implantable cardioverter-defibrillator therapy: a national survey in Danish health-care professionals.

AIMS: The aim of this study was to examine health-care professionals attitudes towards implantable cardioverter-defibrillator (ICD) therapy and issues discussed with patients. METHODS AND RESULTS: Survey of 209 health-care professionals providing specialized treatment and care of ICD patients at the five implanting centres in Denmark. Questions pertained to gender, age, years of experience within the field, knowledge of the ongoing critical debate on ICD therapy, and personal experience with ICD treatment, and/or sudden cardiac arrest within family and/or friends. Of all participants, 185 (88.5%) completed the survey. Physicians spent less time informing patients about ICD treatment prior to implantation (mean min = 17.7 ± 11.2 vs. 28.6 ± 19.4; P < 0.001). They were more likely to discuss clinical issues but less likely to discuss psychosocial issues with patients compared with non-physicians. Physicians were less likely to believe that their personal attitude towards ICD treatment has no influence on how they deal professionally with patients (27.8 vs. 43.6%; P = 0.04). Physicians and non-physicians were equally positive towards ICD therapy as primary prophylaxis in ischaemic cardiomyopathy (87.6 vs. 82.1%; P = 0.40) but not in non-ischaemic cardiomyopathy (57.3 vs. 83.9%; P < 0.001). Physicians were more positive towards ICD therapy as secondary prophylaxis (98.9 vs. 84.2%; P = 0.001) compared with non-physicians. CONCLUSIONS: Physicians focus on clinical rather than psychosocial issues when discussing ICD treatment with candidate patients. At the same time, physicians are more aware that their attitude towards ICD treatment may influence how they deal professionally with patients compared with non-physicians.

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.

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

BACKGROUND: 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. AIM: To determine the molar relation of BNP-32 and proBNP in different cardiovascular regions. METHODS AND RESULTS: Blood samples were obtained from different cardiovascular regions during right heart catheterization in heart failure patients, and from normal subjects. Plasma BNP-32 and proBNP concentrations were measured using sequence-specific radioimmunoassays. Patients with severe left ventricular dysfunction (n=21) displayed increased peripheral plasma concentrations of both BNP-32 (four-fold, P=0.0008) and proBNP (seven-fold, P=0.0002) compared with normal subjects. Moreover, the peripheral concentrations were highly correlated with the corresponding concentrations in the coronary sinus (BNP-32: r=0.97, P<0.0001; proBNP: r=0.94, P<0.0001). Despite comparable peripheral concentrations of BNP-32 and proBNP, the BNP-32 concentration was higher than the proBNP concentration in the coronary sinus (median 126 pmol/l (21-993) vs. 103 pmol/l (16-691), P=0.035). CONCLUSIONS: The BNP-32 and proBNP concentrations are closely related in venous cardiac blood. The findings suggest an overall constitutive secretion of processed proBNP, i.e. an N-terminal precursor fragment and BNP-32, in chronic heart failure.

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.

[Yield of a coronary arteriography database. A study of 5.536 registrations at the cardiologic laboratory, Rigshospitalet]. / Udbyttet af en database over koronararteriografier. En opgørelse af 5.536 registreringer på kardiologisk laboratorium, Rigshospitalet.

INTRODUCTION: Coronary arteriography (CAG) is an expensive investigation that provides potentially valuable information, but also carries a risk of severe complications. It is therefore natural to examine the usefulness of an existing database on CAG. METHODS: The analysis covers all registrations of CAG entered into the database at the Heart Centre at Rigshospitalet, Copenhagen, from April 1999 to September 2000. RESULTS: Altogether, 5536 CAGs were registered. The indication was stable coronary artery disease in 52.0% and acute ischaemic heart disease in 25.5%. As an example of the medical information available from the data base, it is notable that left main coronary stenosis or three-vessel disease, conditions in which coronary bypass surgery increases long-term survival, was found in 42.4% of patients with angina pectoris in Canadian Cardiovascular Society (CCS) class 4, but also in 24.4% of patients in CCS class 1. DISCUSSION: Clinical databases, such as the one presented, can ensure that all relevant information is stored, and in this case even results in enhanced effectiveness, because data may be directly transformed into other formats, such as charts. The database furthermore provides clinical information, for instance that the severity of angina pectoris cannot identify the most ill patients in whom a CABG is potentially life-prolonging. In addition, the database provides administrative data that is used in the training of doctors, evaluation of referral patterns, surveillance of complications, and in the daily administration and planning.

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 (Spearman's 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.

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.

[Safety of magnetic resonance imaging in patients with pacemaker and implantable defibrillator]. / Sikkerhed af magnetisk resonans-skanning hos patienter med pacemaker og implanterbar defibrillator.

INTRODUCTION: The presence of a cardiac implantable device is ICD considered an absolute contraindication to magnetic resonance imaging (MRI). The purpose of this study was to evaluate the safety of performing MRI in patients with cardiac pacemakers and ICDs that had a compelling clinical need for MRI examination. MATERIAL AND METHODS: During a period of nine years we have included 65 patients with cardiac devices (60 pacemakers and five ICDs) who underwent a total of 73 MRI examinations at 1.5 T. All pacemakers were reprogrammed before MRI to asynchronous mode to avoid MRI-induced inhibition or to sense only mode to avoid MRI-induced competitive pacing and potential pro-arrhythmia. All devices were interrogated immediately before and after the MRI examination, which included measurement of sensitivity, pacing capture threshold (PCT) and lead impedance. RESULTS: MRI examinations were completed safely in 63 patients. Inhibition of pacemaker output was observed in one patient and induction of ventricular fibrillation was observed in another with ICD. A significant increase in PCT was rare and only detected in 1% of all electrodes. CONCLUSION: MRI can be performed safely in patients with pacemakers with an acceptable risk-benefit ratio, while MRI of patients with ICDs must still be considered an experimental procedure.

Sarcoidosis-associated pulmonary hypertension: acute vasoresponsiveness to inhaled nitric oxide and the relation to long-term effect of sildenafil.

BACKGROUND: Severe pulmonary sarcoidosis is often complicated by pulmonary hypertension (PH) caused by different pathophysiological mechanisms. OBJECTIVES: To assess the acute vasoresponsiveness in patients with sarcoidosis and PH and the relation to the therapeutic effect of sildenafil. METHODS: A retrospective chart review of 25 patients with recalcitrant pulmonary sarcoidosis being evaluated for lung transplantation at our centre. Haemodynamics were evaluated by right heart catheterisation in 24 patients of whom 19 had PH. Eight of the 19 patients received vasodilator challenge with inhaled nitric oxide (iNO). RESULTS: The study group of eight patients (seven men) had a median age of 51 years (range 38 years-58 years). During iNO we observed a reduction in all patients' mean pulmonary arterial pressure (MPAP) of median 9 mmHg (range 1 mmHg-20 mmHg) (P = 0.01) and in all patients' pulmonary vascular resistance of median 2.0 Wood Units (0.7 Wood Units-5.8 Wood Units) (P = 0.01). Acute vasoresponsiveness defined as reduction in MPAP of >or=10 mmHg to a MPAP of

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.

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.

Non-invasive measurement of cardiac output in heart failure patients using a new foreign gas rebreathing technique.

Values of effective pulmonary blood flow (Q(EP)) and cardiac output, determined by a non-invasive foreign gas rebreathing method (CO(RB)) using a new infrared photoacoustic gas analysing system, were compared with measurements of cardiac output obtained by the direct Fick (CO(FICK)) and thermodilution (CO(TD)) methods in patients with heart failure or pulmonary hypertension. In 11 patients, of which three had shunt flow through areas without significant gas exchange, the mean difference (bias) and limits of agreement (+/- 2 S.D.) were 0.6 +/- 1.2 litre x min(-1) when comparing CO(FICK) and Q(EP), and -0.8 +/- 1.3 litre x min(-1) when comparing CO(FICK) and CO(TD). When correction for intrapulmonary shunt flow was applied (i.e. calculation of CO(RB)) in all 11 patients, the bias between CO(FICK) and CO(RB) was 0.1 +/- 0.9 litre x min(-1), primarily because agreement improved in the three patients with significant shunt flow. In the eight patients without significant shunt flow, the agreement between Q(EP) and CO(FICK) was 0.3 +/- 0.9 litre x min(-1). In conclusion, a foreign gas rebreathing method with a new infrared photoacoustic gas analyser provided at least as reliable a measure of cardiac output as did thermodilution. In the absence of significant shunt flow, measurement of Q(EP) itself provides a reliable estimate of cardiac output in heart failure patients. The infrared photoacoustic gas analyser markedly facilitates clinical use of the rebreathing method in general, which makes the method available to a larger group of clinicians working with patients with cardiovascular diseases.