Markus Schönburg

Progression From Compensated Hypertrophy to Failure in the Pressure-Overloaded Human Heart Structural Deterioration and Compensatory Mechanisms

Background—The progression of compensated hypertrophy to heart failure (HF) is still debated. We investigated patients with isolated valvular aortic stenosis and differing degrees of left ventricular (LV) systolic dysfunction to test the hypothesis that structural remodeling, as well as cell death, contributes to the transition to HF. Methods and Results—Structural alterations were studied in LV myectomies from 3 groups of patients (group 1: ejection fraction [EF] >50%, n=12; group 2: EF 30% to 50%, n=12; group 3: EF <30%, n=10) undergoing aortic valve replacement. Control patients were patients with mitral valve stenosis but normal LV (n=6). Myocyte hypertrophy was accompanied by increased nuclear DNA and Sc-35 (splicing factor) content. ACE and TGF-&bgr;1 were upregulated correlating with fibrosis, which increased 2.3-, 2.2-, and 3.2-fold over control in the 3 groups. Myocyte degeneration increased 10, 22, and 32 times over control. A significant correlation exists between EF and myocyte degeneration or fibrosis. Ubiquitin-related autophagic cell death was 0.5‰ in control and group 1, 1.05 in group 2, and 6.05‰ in group 3. Death by oncosis was 0‰ in control, 3‰ in group 1, and increased to 5‰ (groups 2 and 3). Apoptosis was not detectable in control and group 3, but it was present at 0.02‰ in group 1 and 0.01‰ in group 2. Cardiomyocyte mitosis was never observed. Conclusions—These structure-function correlations confirm the hypothesis that transition to HF occurs by fibrosis and myocyte degeneration partially compensated by hypertrophy involving DNA synthesis and transcription. Cell loss, mainly by autophagy and oncosis, contributes significantly to the progression of LV systolic dysfunction.

Transapical aortic valve implantation using a new self-expandable bioprosthesis (ACURATE TA ™ ): 6-month outcomes †

OBJECTIVESnThe ACURATE TA(™) Aortic Bioprosthesis and Delivery System (Symetis S.A., Ecublens, Switzerland) is a new transcatheter aortic valve designed for transapical implantation. The six-month results from the completed first-in-man study are reported.nnnMETHODSnThe Symetis ACURATE TA(™) is composed of a porcine biological tissue valve attached to a self-expandable nitinol stent. It allows for anatomical orientation and facilitates intuitive implantation providing tactile feedback. Since November 2009, a total of 40 high-risk elderly patients have been treated.nnnRESULTSnThe mean age of enrolled patients was 83.2 ± 4.0; 60.0% were female, with a mean logistic EuroSCORE of 21.2 ± 10.8% and a mean Society of Thoracic Surgeons (STS) score of 9.0 ± 4.7%. All implants were delivered successfully in the intra-annular and subcoronary position. One patient was converted to conventional surgery due to coronary impingement (after valve-in-valve implantation). One additional patient received valve-in-valve treatment (SAPIEN THV TA(™)). Five patients expired within 30 days and two additional patients expired during the 6-month follow-up due to non-valve-related causes resulting in a mid-term survival rate of 82.5%. Two patients suffered a stroke and another three required new onset pacemaker implantation. The mean aortic gradient significantly improved and remained stable throughout the follow-up (baseline: 51.9 ± 14.3 mmHg, 30 days: 12.3 ± 5.1 mmHg, 6 months: 11.9 ± 5.8 mmHg). At the 6-month follow-up, 96.7% of patients demonstrated either none/trace or mild (1+/4) paravalvular leakage only. According to the Valve Academic Research Council the devices success rate was 92.5%, with a 30-day safety profile of 25%.nnnCONCLUSIONSnAt the 6-month follow-up, the ACURATE TA(™) device showed stable valve function with low rates of paravalvular leakages. The cohort of high-risk patients demonstrated good clinical outcomes and 6-month survival.

Anemia Before Coronary Artery Bypass Surgery as Additional Risk Factor Increases the Perioperative Risk

BACKGROUNDnA negative relationship between anemia before coronary artery bypass graft (CABG) surgery and the perioperative mortality has been shown. We tried to clarify whether anemia only expresses an increased perioperative risk or is a risk factor per se in a two-institution database.nnnMETHODSnIn the years 2005 and 2006, 185 of 3,311 patients undergoing isolated first-time CABG surgery had anemia defined as hematocrit less than 33% or Hb≤11 g/dL. Preoperative and postoperative data of patients having anemia and patients having normal hematocrit were compared using χ2-tests or Fishers exact tests regarding structural group differences. To determine factors influencing perioperative mortality, methods of logistic regression were used.nnnRESULTSnThe 30-day mortality of anemic patients (12.9%) was significantly higher (p<0.001) than the mortality of nonanemic patients (2.2%). Patients having anemia, though, had a worse risk profile before surgery: high European System for Cardiac Operative Risk Evaluation values (median, 7 in anemic patients versus 4 in nonanemic patients), acute myocardial infarction (9.7% in anemic versus 2% in nonanemic patients), diabetes mellitus (45.4% in anemic versus 33.3% in nonanemic patients), and cardiogenic shock (5.4% in anemic versus 0.8% in nonanemic patients) were significantly more frequent in the anemic group. However, taking these risks in account, the logistic regression revealed preoperative anemia still to be a mortality-increasing factor in patients undergoing CABG surgery (odds ratio 3.727, confidence interval: 2.196 to 6.324). Furthermore, anemia was a risk factor for perioperative morbidity (major adverse cardiovascular events) after CABG surgery (odds ratio 2.199, confidence interval: 1.423 to 3.397).nnnCONCLUSIONSnIn our patient group undergoing CABG surgery, preoperative anemia increased the mortality risk by 3.4, even when taking the higher perioperative risk of anemic patients into consideration.

Short- and long-term outcomes in octogenarians after coronary artery bypass surgery.

OBJECTIVESnCoronary artery surgery in octogenarians is carried out with an increasing frequency. We tried to determine short- and long-term outcomes and quality of life after coronary artery surgery in this patient group.nnnMETHODSnFrom 3312 patients undergoing isolated coronary artery bypass graft (CABG) surgery in two centres in the years 2004-06, 240 (7.2%) were older than 80 years (mean age 82.3 years, 57.1% male). The octogenarians were analysed regarding perioperative major adverse cardiac and cerebrovascular events (MACCE), late mortality and health-related quality of life (SF-12 questionnaire) and compared with 376 younger patients (mean age 66.8 years, 61.4% male) using propensity score matching. The mean follow-up time of 30-day survivors was 53 months, and follow-up completeness was 97.1%.nnnRESULTSnThe octogenarians 30-day mortality rate was 6.8% (vs 1.6% in the younger group). In the multivariate analysis, age was a risk factor for early death [odds ratio (OR) 4.28, 95% confidence interval (CI): 1.59-11.53] and perioperative MACCE (OR 2.78, 95% CI:1.44-5.37). One-year and 3-year survivals were 94.5 and 81.4% in the octogenarians and 98 and 91.3% in the younger group. Four years after surgery, 95.2% of the octogenarians lived alone, with a partner or with relatives, and only 4.0% required permanent nursing care. 83.9% of the octogenarians would recommend surgery to their friends and relatives for relief of symptoms.nnnCONCLUSIONSnOctogenarians can undergo CABG surgery with an acceptable risk of early death. Though late mortality is high, late quality of life is comparable with that of younger patients.

Coronary stenting before coronary artery bypass graft surgery in diabetic patients does not increase the perioperative risk of surgery.

OBJECTIVEnA negative relationship between coronary stenting before coronary artery bypass graft (CABG) surgery and the perioperative mortality and morbidity has been shown in diabetic patients. We tried to assess this relationship in a 2-institution database.nnnMETHODSnIn the years 2005 and 2006, 1125 of 3311 patients undergoing CABG surgery had diabetes mellitus (33.9%), and 185 (16.4%) of the diabetic patients had at least 1 previous stent. There was no evidence of any clinically significant difference in the preoperative and intraoperative parameters between diabetics with or without previous stents.nnnRESULTSnThirty-day mortality (no-stent group, 3.86%; stent group, 1.62%) and postoperative major adverse cardiovascular and cerebrovascular events (MACCEs; mortality, stroke, myocardial infarction, renal failure) (no-stent group, 12.2%; stent group, 5.9%) occurred more often in diabetic patients without coronary stents. Logistic regression for 30-day mortality using possible confounders including preoperative stent showed a significant positive effect of preoperative coronary stenting (OR, 0.157; 95% CI limits, 0.033-0.737). Taking percutaneous coronary intervention out of the calculation model, this positive effect was no longer significant (OR, 0.344; CI, 0.091-1.298). Logistic regression for perioperative MACCE, with as well as without percutaneous coronary intervention as a confounder, also showed a significant positive effect of preoperative coronary stenting (OR,xa00.231; 95% CI, 0.091-0.590).nnnCONCLUSIONSnCoronary stenting before CAGB in diabetic patients does not predispose to a higher perioperative risk regarding mortality and morbidity after CABG surgery.

Aneurysm Formation After Patch Aortoplasty Repair (Vossschulte): Reoperation in Adults With and Without Hypothermic Circulatory Arrest

BACKGROUNDnAortic aneurysm formation is common after patch aortoplasty repair of coarctation of the aorta. Its incidence varies between 5% and 38%. The majority of patients show progressive aneurysmal dilation within 6 to 18 years and reoperation is necessary to avoid rupture of the aneurysm.nnnMETHODSnTen patients were reoperated on for patch aneurysm formation. Femorofemoral cardiopulmonary bypass (CPB) with a heparinized system was used in all patients. Decision to initiate hypothermic circulatory arrest (HCA) was made intraoperatively. All patients received a Dacron graft replacement of the aneurysmatic thoracic aorta.nnnRESULTSnHCA was initiated in 5 patients owing to extreme adhesions in vicinity to the aneurysm. There was no significant intergroup difference regarding time interval after first operation, age, operation time, and postoperative blood loss. Only minor neurologic events were present in 2 patients with cross-clamping the aorta.nnnCONCLUSIONSnPatch aneurysms after Vossschulte aortoplasty can safely be operated on with femorofemoral CPB. Initiation of HCA is recommended to prevent rupture of the aneurysm during preparation and injury of adjacent nerves and vessels.

High-dose enoximone to evaluate reversibility of pulmonary hypertension : Is there a diagnostic value of neurohormonal measurements?

BACKGROUNDnHeart transplantation is associated with a reduction of the neurohumoral activation seen in patients with severe congestive heart failure. In this study, we investigated whether pharmacologically induced complex hemodynamic improvement during assessment of reversibility of pulmonary hypertension with a phosphodiesterase inhibitor is able to induce neurohormonal changes of diagnostic importance.nnnMETHODS AND RESULTSnTwenty-one patients with New York Heart Association class III-IV heart failure underwent infusion of 3 mg/kg enoximone over a period of 30 minutes. Before and after drug infusion, we determined the plasma concentrations of atrial natriuretic peptide, endothelin-I, angiotensin-II, aldosterone, norepinephrine, epinephrine, and angiotensin-converting enzyme activity sampled from a peripheral vein and the pulmonary artery. In addition to the expected significant reduction of pulmonary hypertension and enhancement of cardiac output, increased levels of the vasoconstrictors endothelin-I, angiotensin-II, and norepinephrine were observed. Aldosterone fell after enoximone infusion; a higher baseline aldosterone level correlated to the degree of reduction of the pulmonary arteriolar resistance by enoximone. Baseline atrial natriuretic peptide levels correlated with parameters, indicating the severity of heart failure. However, the plasma concentration of this peptide did not change significantly after enoximone infusion.nnnCONCLUSIONSnAcute hemodynamic improvement after enoximone bolus in candidates for heart transplantation is not accompanied by a reduction of the enhanced neurohumoral activity in these patients. The reaction of the investigated hormones cannot predict the individual degree of reversibility of pulmonary hypertension.

Valve surgery combined with coronary artery operation: is the use of internal mammary artery a predictor for early complications?

The internal mammary artery (IMA) provides better early and long-term patency than venous grafts do. Although IMA is the conduit of choice in isolated coronary artery bypass grafting (CABG), its use in combined procedures is not routine in some cardiovascular units. During a 16-month period, 188 patients underwent valve surgery combined with CABG. Internal mammary grafts were used in 68/188 (36%) patients (group 1) and vein grafts without arterial grafts (group 2) in 120/188 (64%). Left IMA was implanted in 67/68 (99%) and right IMA in 1/68 1%) cases. Surgeon A used IMA in 28/44 (64%), surgeon B in 20/32 (63%), surgeon C in 18/44 (41%), surgeon D in 1/4 (25%) and surgeon E in 1/63 (2%) patients. The final decision to use IMA in a combined procedure was left up to the surgeon. Statistically, the preoperative- and perioperative data were identical in the two groups, although the frequency of IMA grafting in patients with double valve replacement and reoperation was lower (1/68 vs 11/120, ns, and 3/68 vs 9/120, ns). Ten of 188 (5.3%) patients died within 30 days after operation. Longer cross-clamp time (P = 0.008) and mitral valve replacement (P = 0.05) were independent risk factors for early death. The use of IMA did not increase the risk of early mortality. The postoperative variables were similar in the IMA and vein groups, in particular data suggesting perioperative myocardial infarction (CK-MB, catecholamine support). Postoperative mechanical ventilation was longer in the IMA group, although not significantly (P = 0.06). Early mortality and morbidity were identical in the two groups in combined procedures. We did not find any hints for an increased risk of using IMA in this type of surgery. Internal mammary artery implantation is safe in selected patients undergoing combined valve and CABG surgery. Beside the better long-term patency of IMA, its use may have several technical advantages.

Thrombotic formations within the aortic arch as source of embolization in patients with coagulopathia

Thrombotic formations on atherosclerotic lesions of the thoracic aorta are potential sources of cerebral and systemic embolization. Especially younger patients without calcifications of atherosclerotic plaques or coagulation disorders have a higher risk for embolization. Magnetic resonance imaging and transesophageal echocardiography are the diagnostic methods of choice. As an alternative to anticoagulation surgical therapy is indicated to prevent severe brain damage or multiorgan failure in patients with mobile thrombotic formations. Herein we describe two patients in whom successful surgical treatment was performed in deep hypothermic circulatory arrest by excision of the aortic arch atheroma.

Animal Models and “Omics” Technologies for Identification of Novel Biomarkers and Drug Targets to Prevent Heart Failure

It is now accepted that heart failure (HF) is a complex multifunctional disease rather than simply a hemodynamic dysfunction. Despite its complexity, stressed cardiomyocytes often follow conserved patterns of structural remodelling in order to adapt, survive, and regenerate. When cardiac adaptations cannot cope with mechanical, ischemic, and metabolic loads efficiently or become chronically activated, as, for example, after infection, then the ongoing structural remodelling and dedifferentiation often lead to compromised pump function and patient death. It is, therefore, of major importance to understand key events in the progression from a compensatory left ventricular (LV) systolic dysfunction to a decompensatory LV systolic dysfunction and HF. To achieve this, various animal models in combination with an “omics” toolbox can be used. These approaches will ultimately lead to the identification of an arsenal of biomarkers and therapeutic targets which have the potential to shape the medicine of the future.