Nedim Selimovic

Three decades of heart transplantation in Scandinavia: long-term follow-up

Heart transplantation (HTx) has become a standard treatment for patients with end‐stage heart disease. The aim of this study was to report the long‐term outcome after HTx in Scandinavia.

Echocardiography can Identify Patients with Increased Pulmonary Vascular Resistance by Assessing Pressure Reflection in the Pulmonary Circulation

Background—Pulmonary hypertension is a frequent finding in patients with cardiopulmonary disorders. It is important to recognize pulmonary hypertension due to increased pulmonary vascular resistance (PVR), as this affects treatment and prognosis. Patients with increased PVR have an increased pulmonary pressure reflection. We hypothesized that pressure reflection can be described by echocardiography and that variables related to pressure reflection can identify patients with increased PVR. Methods and Results—The study comprised 98 patients investigated within 24 hours of right heart catheterization and 20 control subjects. The pressure reflection variables were obtained by pulsed Doppler in the pulmonary artery and continuous Doppler of tricuspid regurgitation. We selected 3 variables related to pressure reflection: the interval from valve opening to peak velocity in the pulmonary artery (AcT, ms), the interval between pulmonary artery peak velocity and peak tricuspid velocity (tPV-PP, ms), and the right ventricular pressure increase after peak velocity in the pulmonary artery (augmented pressure, AP, mm Hg). The correlation between simultaneous catheter- and echocardiography-determined AP was strong (n=19, R=0.83). The AcT, tPV-PP, and AP in patients with a PVR of >3 Woods units (n=71) was (mean±SD) 77±16 ms, 119±36 ms, and 22±12 mm Hg, respectively, and differed from patients with a PVR of ≤3 Woods units (n=27, P<0.0001), 111±32 ms, 39±54 ms, and 3±4 mm Hg, and from controls, 153±32 ms, −19±45 ms, and 0 mm Hg, respectively (P<0.0001). The AcT, tPV-PP, and AP values were not correlated with capillary wedge pressure (R=0.08–0.16). The areas under the receiver operator characteristic curve (95% CI) for AcT, tPV-PP, and AP were 0.87 (0.82 to 0.95), 0.94 (0.89 to 0.99), and 0.98 (0.95 to 1.0), respectively. Conclusions—In this study, we describe a novel echocardiography method for assessing pressure reflection in the pulmonary circulation. This method can be used to identify patients with pulmonary hypertension due to increased PVR.

Pulmonary hemodynamics as predictors of mortality in patients awaiting lung transplantation

Lung transplantation (LTx) is a therapeutic option for patients with end‐stage lung disease. However, the mortality rate of patients on the waiting list is high. The purpose of this study was to examine the prognostic value of cardio‐pulmonary hemodynamics for death in patients awaiting LTx. Retrospectively, 177 patients with advanced lung disease accepted for LTx at Sahlgrenska University Hospital from January 1990 through December 2003 were studied. Patient demographics, pulmonary function tests, gas exchange and hemodynamic variables were included in the analysis. Death while awaiting LTx was the primary endpoint for all analyses. Mean age was 49 ± 9 years. Main diagnoses were alpha 1 antitrypsin deficiency (n = 56), chronic obstructive pulmonary disease (n = 61), cystic fibrosis (n = 14) and interstitial lung disease (n = 46). Thirty patients died (17%). LTx was performed in 143 cases. By univariate analyses, forced vital capacity (FVC) % of predicted, pulmonary vascular resistance (PVR) and diagnosis were associated with risk for death. In multivariate analysis PVR (HR, 1.22; 95% CI, 1.06–1.41; P = 0.006) and FVC% of predicted (HR, 0.97; 95% CI, 0.94–0.99; P = 0.01) were independently associated with death. Patients with increased PVR and a lower FVC % of predicted awaiting LTx should be considered for a higher organ allocation priority. Assessment of pulmonary hemodynamics needs to be considered during evaluation for LTx.

Fatal Dilated Cardiomyopathy Associated with a Mitochondrial DNA Deletion

A 27-year-old man was admitted to hospital because of severe cardiac failure. Investigation revealed dilated cardiomyopathy with a left ventricular ejection fraction of 15–20%. During adolescence the patient had been investigated for growth retardation and he also had progressive external ophthalmoplegia. There had been no symptoms of cardiac disease until 2 weeks before admittance. An endomyocardial biopsy showed cardiomyocytes deficient in cytochrome c oxidase (COX) in a mosaic pattern. A skeletal muscle biopsy showed mitochondrial myopathy with COX-deficient ragged-red fibers. Molecular genetic analysis revealed a heteroplasmic, 3.8-kb, mitochondrial DNA (mtDNA) deletion in heart and muscle. PCR-based quantification of the proportion of mtDNA with deletion showed 47% mutated mtDNA in the myocardial biopsy and 68% in muscle. In spite of treatment, the condition deteriorated and the patient died 5 days after admittance. This case demonstrates that mtDNA deletions may occasionally be the cause of severe dilated cardiomyopathy, and that morphological and molecular genetic diagnosis may be obtained by endomyocardial biopsy.

Doppler echocardiography can provide a comprehensive assessment of right ventricular afterload.

BACKGROUND The purpose of this study was to evaluate novel Doppler echocardiographic methods for a comprehensive assessment of right ventricular afterload, including pulmonary artery (PA) mean pressure (PAMP) and the PA pressure waveform. METHODS The study comprised 109 patients who underwent right-heart catheterization simultaneously (group A, n = 31) with Doppler echocardiography on 35 occasions or nonsimultaneously (group B, n = 78) within 24 hours of Doppler echocardiography. Right ventricular afterload variables were obtained using pulsed Doppler in the PA and continuous Doppler of tricuspid regurgitation. The intervals from QRS to the opening and closing of the pulmonary valve and to the peak velocity of tricuspid regurgitation were measured. PA end-diastolic pressure, PA systolic pressure, and PA notch pressure were calculated. The Doppler-derived pressure curve was separated into 3 parts with fitted second-order curves. RESULTS Catheter PAMP and Doppler PA systolic pressure in group A were strongly related (R = 0.85). The regression equation from group A (PAMP = 0.65 x Doppler PA systolic pressure - 1.2 mm Hg) was used to calculate PAMP in group B. There was no difference between catheter PAMP (mean, 39 +/- 18 mm Hg; range, 8-95 mm Hg) and Doppler PAMP (mean, 39 +/- 15 mm Hg; range, 12-83 mm Hg) (P = .85). The systolic areas under the curves for catheter and Doppler PAMP in group A were 20 +/- 4.7 and 20 +/- 4.0 mm Hg s, respectively (P = .52), and the diastolic areas were 21 +/- 5.7 and 22 +/- 6.3 mm Hg s, respectively (P = .21). CONCLUSION A comprehensive assessment of right ventricular afterload that includes PAMP and the PA pressure waveform can be provided by Doppler echocardiography in patients with a wide range of PA pressures and different diagnoses.

Tricuspid regurgitation influences outcome after heart transplantation

BACKGROUND We investigated the correlation between tricuspid regurgitation (TR) and late survival, and its relation to bicaval (BC) and biatrial (BA) technique, after heart transplantation (HTx). METHODS HTx was performed in 464 patients between 1984 and 2009 at Sahlgrenska University Hospital. The BA technique was mostly performed in the early experience and BC in the late experience. Most patients underwent echocardiograms, and data for TR were retrospectively gathered at discharge and at the 5-year and 10-year follow-up. Survival with regard to surgical technique and to post-operative TR was analyzed. RESULTS The BC technique resulted in less early TR (p < 0.001). This difference was still observed among survivors at 5 years (p = 0.013) but not at 10 years (p = 0.082). A multivariate logistic regression analysis found the BA technique was the only predictor of early moderate to severe TR (odds ratio, 2.70; 95% confidence interval, 1.68-4.32; p < 0.001). Furthermore, when time era was introduced, it became the only significant predictor, with a lower risk to develop moderate to severe early post-operative TR in more recent eras. There was no significant difference in long-term survival between the 2 surgical technique groups. However, stratified for TR at discharge, patients with mild or no TR had better survival than those with moderate or severe TR (p < 0.01). CONCLUSIONS The BC technique results in less TR early post-operatively. The BA technique and/or time era seem to predict the occurrence of early moderate to severe TR. Regardless of the technique used, patients with moderate or severe TR at discharge have an increased mortality during the first 5 years.

Right ventricular ejection fraction during exercise as a predictor of mortality in patients awaiting lung transplantation: a cohort study.

Objective The occurrence of right ventricular dysfunction is a well-known indicator of poor prognosis in patients with chronic cardiopulmonary disease. The role of right ventricular ejection fraction (RVEF) at rest and during exercise as predictors of outcome in patients awaiting lung transplantation (LTx) is unclear. Design We performed a retrospective analysis of lung transplant candidates who had undergone equilibrium radionuclide angiography (ERNA), to determine baseline and exercise RVEF. Lung function, gas exchange and pulmonary haemodynamics were also assessed. Patients and main outcome measures 152 patients (mean age 47±11 years; 59% women) were included in the study. Primary endpoint was death on the waiting list for LTx. Main diagnoses were α-1 antitrypsin deficiency (n=35), chronic obstructive pulmonary disease (n=41), cystic fibrosis (n=10), interstitial lung disease (n=34) and pulmonary arterial hypertension (n=32). Twenty-five patients died (16, 4%). LTx was performed in 121 patients. The mean RVEF at rest was equal to mean RVEF during exercise (38±12%). In univariate analysis RVEF at rest, RVEF during exercise, heart rate and forced volume capacity (FVC) % of predicted were factors significantly associated with risk of death. In multivariate analysis RVEF during exercise and FVC% of predicted were independent predictors of death. Conclusions In lung transplant candidates, right ventricular function during exercise is a stronger predictor of outcome than right ventricular function at rest. RVEF during exercise assessed by ERNA could be incorporated into priority-based allocation algorithms for LTx.

Adaptation and validation of the Cambridge pulmonary hypertension outcome review for Sweden

Background: The Cambridge pulmonary hypertension outcome review (CAMPHOR) is the first pulmonary hypertension-specific instrument for the assessment of the patient’s perceived symptoms, activity limitations and quality of life (QoL). Purpose: To produce and validate a Swedish language version of the CAMPHOR. Methods: Bilingual (n = 5) and lay panels (n = 5) were conducted to translate the CAMPHOR into Swedish. This new questionnaire was then field-tested with 14 patients and finally, it underwent psychometric evaluation by means of a postal validation study involving 38 patients with pulmonary hypertension (PH). Results: Few problems were experienced in translating the CAMPHOR into Swedish. The field-test participants found the scales relevant, comprehensible and easy to complete. Psychometric analyses showed that the Swedish adaptation was successful. The Swedish CAMPHOR scales had good internal consistency. Cronbach’s alpha coefficients were 0.92 for the symptoms scale, 0.92 for activity limitations and 0.95 for the quality of life. Predicted correlations with the Nottingham Health Profile provided evidence of the construct validity of the scales. The Swedish scales also indicated known groups validity. Conclusions: The Swedish version of the CAMPHOR is a reliable and valid measure of the impact of pulmonary hypertension on the lives of affected patients. It is recommended for use in clinical studies and routine practice in pulmonary hypertension patients.

Extracorporeal membrane oxygenation as a bridge to lung transplantation in a patient with persistent severe porto-pulmonary arterial hypertension following liver transplantation

Idiopathic pulmonary artery hypertension (IPAH) is a progressive disease with a dismal prognosis and lung transplantation is often the only option for patients, who do not respond to pharmacological therapy. We report the use of an extracorporeal membrane oxygenation (ECMO) system in a 49-year-old woman with primary pulmonary hypertension, previously liver transplanted. The patient, listed for lung transplantation, developed respiratory and circulatory failure despite maximal pharmacological therapy and was successfully bridged to emergent bilateral lung transplantation with veno-arterial ECMO. Emergent veno-arterial ECMO was able to rescue the patient and bridge her to bilateral lung transplantation and should therefore be an option for patients with PAH and circulatory collapse.

305 Adaptation and Validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for Sweden

Pulmonary hypertension (PH) is a chronic disease which severely impairs quality of life (QoL). The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific tool to assess patient-reported symptoms, functioning and QoL in PH patients. The aim of this study was to adapt and validate the CAMPHOR for use in Croatia. The adaptation process involved three stages: translation (bilingual and lay panel), cognitive debriefing interviews with patients and psychometric validation. For the latter stage, a postal survey was conducted with 50 patients to examine the reliability and validity of the adapted scale. All three scales of the Croatian CAMPHOR demonstrated excellent internal consistency (Symptoms = 0.93; Activity limitations = 0.94; QoL = 0.92) and test-retest reliability correlations (Symptoms = 0.90; Activity limitations = 0.95; QoL = 0.90). Predicted correlations with the SF-36 scales provided evidence for construct validity of the CAMPHOR scales. Evidence for known group validity was shown by the ability of the scales to distinguish between participants based on patient-perceived general health and disease severity. The Croatian version of the CAMPHOR is a valid and reliable tool for use in clinical routine and clinical research.