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- Granfeldt, Hans, 1960-
(författare)
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The use of mechanical circulatory support and passive ventricular constraint in patients with acute and chronic heart failure
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many patients are diagnosed as having chronic heart failure (CHF) and apart from the fact that daily activities are impaired, they are great consumers of health care, and the prognosis is poor. The distinction between acute heart failure (AHF) and CHF may be difficult and is more a question of time rather than severity. The “gold standard” treatment for end‐stage heart failure is heart transplantation. Due to organ shortage this is reserved for selected patients only. Since the introduction of mechanical circulatory support (MCS) more and more patients with progressive CHF have been bridged‐to‐heart‐transplantation. There are MCS systems available for both short‐ and long‐term support. Newer concepts such as ventricular constraint to prevent ventricular remodelling are on the way. We have investigated short‐ (ImpellaTM) and long‐term (HeartMateTM I and II) MCS and ventricular constraint (CorCapTM CSD) as treatment concepts for all forms of heart failure, the aims being: bridge‐to‐decision, bridge‐to‐transplant and extended therapy, called “destination therapy” (DT).Methods and results: In Paper I, the use of HM‐ITM pulsatile MCS in bridge‐to‐transplantation patients in Sweden was retrospectively investigated regarding outcome and risk factors for mortality and morbidity. Fifty‐nine patients were treated between 1993 and 2002. The dominating diagnosis was dilated cardiomyopathy in 61%. Median support time was 99.5 days. 18.6% died before transplantation. Four patients needed RV assist due to right ventricular failure. Haemorrhage was an issue. Six patients (10%) suffered a cerebrovascular thromboembolic lesion. 15% developed driveline infection. 45% of the MCS patients were discharged home while on pump treatment. Massive blood transfusion was a predictor for mortality and morbidity, p<0.001.In Paper II the second generation long‐term MCS, the continuous axial flow pump HM‐IITM, was prospectively evaluated for mortality and morbidity. Eleven patients, from 2005 until 2008, were consecutively included at our institution. One patient received the pump for DT. The median pump time was 155 days. Survival to transplantation was 81.8%. Ten patients could be discharged home before transplantation after a median time of 65 days.Paper III investigated the Swedish experience and outcome of short‐term axial flow MCS, the ImpellaTM, in patients with AHF. Fifty patients were collected between 2003 and 2007 and divided into two groups: 1. Surgical group (n=33) with cardiogenic shock after cardiac surgery; and 2. Non‐surgical group (n=17), patients with AHF due to acute coronary syndromes with cardiogenic shock (53%) and myocarditis (29%). The 1‐year survival was 36% and 70%, respectively. 52% were reoperated because of bleeding. Predictors for survival at 30 days were preoperatively placed IABP (p=0.01), postoperatively cardiac output at 12 hours and Cardiac Power Output at 6 and 12 hours.In Paper IV we evaluated the use and long term outcome of ventricular constraint CorCapTM CSD. Since 2003, 26 consecutive patients with chronic progressive heart failure were operated with CSD via sternotomy (n=25) or left mini‐thoracotomy (n=1). Seven patients were operated with CorCapTM only. Nineteen patients had concomitant cardiac surgery. There were three early and three late deaths. The remaining cohort (n=18) was investigated in a cross‐sectional study regarding QoL with SF‐36. There was no difference in QoL measured with SF‐36 after a mean 3‐years follow up period, when compared to an age‐ and sex‐matched control group from the general population. The one‐year survival was 86%, and after three years 76%. Echocardiographic dimensions had improved significantly after three years.Conclusion: In our unit, a non‐transplanting medium‐sized cardiothoracic department, short‐ and long‐term MCS (ImpellaTM resp. HMTM) in patients with acute or chronic HF have been used with good results. The use of ventricular constraint early in the course of the disease is a good adjunct to other treatment options in progressive chronic HF patients.
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| 2. |
- Ivert, Torbjörn, et al.
(författare)
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Similar survival 15 years after coronary artery surgery irrespective of left main stem stenosis
- 2013
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006 .- 1651-2510. ; 47:1, s. 42-49
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To evaluate 15-year survival after coronary artery bypass grafting (CABG) in relation to grade left main stenosis (LMS) and right coronary artery (RCA) obstruction. Design. Coronary angiographic findings were prospectively collected in 977 patients who had CABG for stable angina during 1994-1995 and were included in the Swedish Coronary Revascularization - Swedish Council of Technology Assessment study. Results. Significant LMS was present in one fifth of the patients and significant RCA obstruction was found in 61% of those with LMS and in 68% of patients without LMS. The patients were categorized as no LMS (Group I), LMS without RCA obstruction (Group II) or significant LMS with significant right coronary artery (RCA) obstruction (Group III). Early mortality did not differ in the three groups and was 1.2, 1.2% and 0.8% in group I, II and III, respectively. Corresponding survival at 15 years was similar 51%, 47% and 47%, respectively. In multivariable analysis older age, smoking, severe angina, positive stress test, hypertension, diabetes mellitus and ejection fraction <50% were risk factors for death at 15 years. Conclusions. Death 15 years after CABG correlated to clinical variables but was not predicted from presence of LMS with or without significant associated RCA obstruction.
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| 3. |
- Nozohoor, Shahab, et al.
(författare)
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Validation of a modified EuroSCORE risk stratification model for cardiac surgery: the Swedish experience.
- 2011
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940. ; 40:1, s. 185-191
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is used to identify patients at high risk for aortic valve replacement (AVR) in whom alternative procedures, such as trans-catheter aortic valve implantation (TAVI), may be appropriate. The aim of the present study was to calibrate and validate the EuroSCORE for different cardiac surgery procedures to improve patient selection for valve surgery. Methods: The study included 46516 patients undergoing open cardiac surgery during 2001-2007. A fivefold cross-validation technique was used to calibrate four different models. Model discrimination was determined by the area under the receiver operating characteristic (ROC) curve and model calibration by the Hosmer-Lemeshow (H-L) test. Results: The actual and predicted 30-day mortality was 3.2%. The discrimination (ROC area) of the calibrated 30-day mortality prediction models was 0.79 for coronary bypass surgery, 0.77 for mitral valve surgery (MVS), and 0.75 for miscellaneous procedures, compared with 0.78 (p=0.199), 0.74 (p=0.077), and 0.72 (p=0.001), respectively, for the original EuroSCORE. The discrimination for AVR was the same for the calibrated and the original EuroSCORE model (0.70). The H-L test gave a p-value of 0.104 for the calibrated and <0.001 for the original EuroSCORE model. Conclusions: A calibration of EuroSCORE resulted in an acceptable predictive capacity for 30-day mortality, and improved discrimination and calibration for MVS and miscellaneous procedures. However, the poor discriminatory for the AVR procedure suggests that the EuroSCORE may not be satisfying for assessing risk prior to TAVI and that more optimized risk stratification models may be needed.
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| 4. |
- Shang, Ming-Mei, et al.
(författare)
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Lim domain binding 2 : a key driver of transendothelial migration of leukocytes and atherosclerosis
- 2014
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 34:9, s. 2068-2077
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Using a multi-tissue, genome-wide gene expression approach, we recently identified a gene module linked to the extent of human atherosclerosis. This atherosclerosis module was enriched with inherited risk for coronary and carotid artery disease (CAD) and overlapped with genes in the transendothelial migration of leukocyte (TEML) pathway. Among the atherosclerosis module genes, the transcription cofactor Lim domain binding 2 (LDB2) was the most connected in a CAD vascular wall regulatory gene network. Here, we used human genomics and atherosclerosis-prone mice to evaluate the possible role of LDB2 in TEML and atherosclerosis.APPROACH AND RESULTS: mRNA profiles generated from blood macrophages in patients with CAD were used to infer transcription factor regulatory gene networks; Ldlr(-/-)Apob(100/100) mice were used to study the effects of Ldb2 deficiency on TEML activity and atherogenesis. LDB2 was the most connected gene in a transcription factor regulatory network inferred from TEML and atherosclerosis module genes in CAD macrophages. In Ldlr(-/-)Apob(100/100) mice, loss of Ldb2 increased atherosclerotic lesion size ≈2-fold and decreased plaque stability. The exacerbated atherosclerosis was caused by increased TEML activity, as demonstrated in air-pouch and retinal vasculature models in vivo, by ex vivo perfusion of primary leukocytes, and by leukocyte migration in vitro. In THP1 cells, migration was increased by overexpression and decreased by small interfering RNA inhibition of LDB2. A functional LDB2 variant (rs10939673) was associated with the risk and extent of CAD across several cohorts.CONCLUSIONS: As a key driver of the TEML pathway in CAD macrophages, LDB2 is a novel candidate to target CAD by inhibiting the overall activity of TEML.
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| 5. |
- Vidlund, Mårten, 1968-
(författare)
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Glutamate for metabolic intervention in coronary surgery : with special reference to the GLUTAMICS-trial
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Myocardial ischemia is a major cause of postoperative heart failure and adverse outcome in coronary artery bypass graft surgery (CABG). Conventional treatment of postoperative heart failure with inotropic drugs may aggravate underlying ischemic injury. Glutamate has been claimed to increase myocardial tolerance to ischemia and promote metabolic and hemodynamic recovery after ischemia. The aim of this work was to investigate if intravenous glutamate infusion given in association with CABG for acute coronary syndrome can reduce mortality and prevent or mitigate myocardial injury and postoperative heart failure. We also wanted to assess neurological safety issues, as a concern with the use of glutamate is that it may act as an excitotoxin under certain conditions.A metabolic strategy for perioperative care was assessed in an observational study on 104 consecutive patients with severe left ventricular dysfunction undergoing CABG. Based on encouraging clinical results, unsurpassed in the literature, the GLUTAMICS-trial was initiated. 861 patients undergoing CABG for acute coronary syndrome were randomly allocated to blinded intravenous infusion of L-glutamicacid solution or saline. The primary endpoint was a composite of postoperative mortality (≤30 days), perioperative myocardial infarction and left ventric ular heart failure in association with weaning from cardiopulmonary bypass. Secondary endpoints included neurological safety issues, degree of myocardial injury,postoperative hemodynamic state, use of circulatory support and cardiac mortality.The event rate was lower than anticipated and the primary endpoint did not differ significantly between the groups. Regarding secondary endpoints there were significant differences compatible with a beneficial effect of glutamate on post-ischemic myocardial recovery. The putative effect of glutamate infusion was seen in more ischemic patients (CCS class IV) and in patients with evident or anticipated LV-failure on weaning from CPB. No evidence for increased incidence of clinical or subclinical neurological injury was found. In conclusion, intravenous glutamate infusion is safe in the dosages employed and could provide a novel and important way of promoting myocardial recovery after ischemic injury.
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