Thomas Voigtländer

Risk of stroke after transcatheter aortic valve implantation (TAVI): a meta-analysis of 10,037 published patients.

AIMS Transcatheter aortic valve implantation (TAVI) represents a novel treatment option for inoperable or high surgical risk patients with severe symptomatic aortic valve disease. Recent randomised studies have raised major safety concerns because of increased stroke/transient ischemic attack (TIA) rates with TAVI compared to medical treatment and conventional aortic valve replacement. We aimed to review all currently published literature and estimate the incidence of periprocedural stroke and outcomes in patients undergoing TAVI. METHODS AND RESULTS Fifty-three studies including a total of 10,037 patients undergoing transfemoral, transapical or trans-subclavian TAVI for native aortic valve stenosis published between 01/2004 and 11/2011 were identified and included in a meta-analysis. Patients were 81.5 ± 1.8-years-old and had a mean logistic EuroSCORE of 24.77 ± 5.60%. Procedural stroke (<24 h) occurred in 1.5 ± 1.4%. The overall 30-day stroke/TIA was 3.3 ± 1.8%, with the majority being major strokes (2.9 ± 1.8%). During the first year after TAVI, stroke/TIA increased up to 5.2 ± 3.4%. Differences in stroke rates were associated with different approaches and valve prostheses used with lowest stroke rates after transapical TAVI (2.7 ± 1.4%). Average 30-day mortality was more than 3.5-fold higher in patients with compared to those without stroke (25.5 ± 21.9% vs. 6.9 ± 4.2%). CONCLUSIONS TAVI was associated with average 30-day stroke/TIA rate of 3.3 ± 1.8% (range 0-6%). Most of these strokes were major strokes and were associated with increased mortality within in the first 30 days.

Gender differences in acute myocardial infarction in the era of reperfusion (the MITRA registry)

There is conflicting information about gender differences in presentation, treatment, and outcome after acute ST elevation myocardial infarction (STEMI) in the era of thrombolytic therapy and primary percutaneous coronary intervention. From June 1994 to January 1997, we enrolled 6,067 consecutive patients with STEMI admitted to 54 hospitals in southwest Germany in the Maximal Individual TheRapy of Acute myocardial infarction (MITRA), a community-based registry. Women were 9 years older than men, more often had hypertension, diabetes mellitus, and congestive heart failure, and had a history of previous myocardial infarction less often. Women had a longer prehospital delay (45 minutes), had anterior wall infarction more often (odds ratio [OR] 1.21; 95% confidence interval [CI] 1.08 to 1.36), and received reperfusion therapy less often (OR 0.83; 95% CI 0.74 to 0.94). The percentage of patients who were eligible for thrombolysis and received no reperfusion was higher in women (OR 1.7; 95% CI 1.56 to 1.89). Women had recurrent angina (OR 1.45; 95% CI 1.23 to 1.71) and congestive heart failure (OR 1.26; 95% CI 1.01 to 1.56) more often. There was a trend toward a higher hospital mortality in women (age-adjusted OR 1.16, 95% CI 0.99 to 1.35; multivariate OR 1.21, 95% CI 0.96 to 1.51), but there was no gender difference in long-term mortality after multivariate analysis (age-adjusted OR 0.95, 95% CI 0.78 to 1.15; multivariate OR 0.93, 95% CI 0.72 to 1.19). Thus, women with STEMI receive reperfusion therapy less often than men. They experience recurrent angina and congestive heart failure more often during their hospital stay. The age-adjusted long-term mortality is not different between men and women, but there is a trend for a higher short-term mortality in women.

Recombinant Growth Hormone Therapy in Patients With Ischemic Cardiomyopathy Effects on Hemodynamics, Left Ventricular Function, and Cardiopulmonary Exercise Capacity

BACKGROUND We studied the effects of recombinant growth hormone (rhGH) on exercise capacity and cardiac function in patients with ischemic cardiomyopathy. METHODS AND RESULTS Seven patients (aged 55+/-9 years) with mild to moderate congestive heart failure (ejection fraction 31+/-4%) who were on standard therapy were included. The patients were studied at baseline, after 3 months of rhGH treatment, and 3 months after rhGH discontinuation. Cardiac function was assessed by exercise capacity, right heart catheterization at rest and after submaximal exercise, MRI, echocardiography, and Holter monitoring. When administered at a dose of 2 IU/d, rhGH doubled the serum concentration of insulin-like growth factor-I. rhGH improved clinical symptoms and exercise capacity significantly (New York Heart Association class 2.4+/-0.5 initially versus 1.4+/-0.5 at 3 months [mean+/-SD], P<0.05; VO2max 13.6+/-3.8 versus 17.4+/-5.4 mL. kg-1. min-1, P<0.05). Additionally, pulmonary capillary wedge pressures at rest and after submaximal exercise were reduced significantly. Cardiac output increased, particularly at rest (5.0+/-1.1 versus 5.8+/-1.3 L/min; P<0.05). Posterior wall thickness was increased (1.08+/-0.1 versus 1. 24+/-0.3 cm; P<0.05), and the end-diastolic and end-systolic volume indexes decreased significantly after rhGH treatment. There was no significant increase in left ventricular ejection fraction. The improvements were partially reversed 3 months after rhGH discontinuation. CONCLUSIONS The administration of rhGH for 3 months in patients with ischemic cardiomyopathy results in significant improvement in hemodynamics and clinical function. The attenuation of left ventricular remodeling persisted 3 months after discontinuation of treatment.

Comparison of Antiplatelet Effects of Aspirin, Ticlopidine, or Their Combination After Stent Implantation

BACKGROUND This study was performed to analyze the influence of either aspirin, ticlopidine, or their combination on platelet activation and aggregation parameters after stent implantation. METHODS AND RESULTS Sixty-one patients with successful implantation of a single Palmaz-Schatz stent in a native coronary artery were randomly assigned to either group A (aspirin 300 mg/d+ticlopidine 2X250 mg/d), group B (ticlopidine 2X250 mg/d), or group C (aspirin 300 mg/d). Platelet activation was evaluated on days 1, 7, and 14 by flow cytometry measurement of expression of CD62p (p-selectin) and the binding of fibrinogen to the platelet surface glycoprotein IIb/IIIa receptor. Platelet aggregation was induced by addition of ADP or collagen. Differences between treatment groups were compared by ANOVA. Between days 1 and 14, we observed a significant decrease in collagen-induced platelet aggregation in group A (62.2+/-2.5% versus 36.9+/-3.1%), whereas an increase was seen in group B (58.3+/-2.5% versus 67.7+/-3.2%) and no change was seen in group C (P<.0001). The ADP-induced aggregation declined significantly in group A (74.7+/-1.4% versus 55.3+/-2.6%), whereas a delayed reduction was seen in group B (72.0+/-3.0% versus 52.6+/-4.2%) and no change was seen in group C (P=.0017). The CD62p expression declined significantly in groups A (68.2+/-2.7% versus 41.3+/-2.7%) and B (64.8+/-2.9% versus 39.3+/-3.5%) but not in group C (P<.0001). Moreover, the fibrinogen binding decreased significantly in group A (61.0+/-4.3% versus 36.3+/-4.2%) and with delay in group B (58.3+/-2.2% versus 39.4+/-3.0%), whereas no alterations were seen in group C (P=.012). CONCLUSIONS Our results demonstrate synergistic and accelerated platelet inhibitory effects of ticlopidine plus aspirin in patients after stent implantation compared with a monotherapy with either ticlopidine or aspirin alone.

Comparison of primary angioplasty with conservative therapy in patients with acute myocardial infarction and contraindications for thrombolytic therapy

The benefit of primary angioplasty in patients with acute myocardial infarction (AMI) and contraindications for thrombolysis compared to a conservative regimen is still unclear. Out of 5,869 patients with AMI registered by the MITRA trial, 337 (5.7%) patients had at least one strong contraindication for thrombolytic therapy. Out of these 337 patients 46 (13.6%) were treated with primary angioplasty and 276 (86.4%) were treated conservatively. Patients treated conservatively were older (70 years vs. 60 years; P = 0.001), had a higher rate of a history with chronic heart failure (14.8% vs. 4.4%; P = 0.053), a higher heart rate at admission (86 beats/min vs. 74 beats/min; P = 0.001), and a higher prevalence of diabetes mellitus (27.1% vs. 12.8%; P = 0.056). Patients treated with primary angioplasty received more often aspirin (91.3% vs. 74.6%; P = 0.012), β‐blockers (60.9% vs. 46.1%; P = 0.062), angiotensin converting enzyme (ACE) inhibitors (71.7% vs. 44%; P = 0.001), and the so‐called optimal adjunctive medication (54.4% vs. 32.3%; P = 0.004). Hospital mortality was significantly lower in patients who received primary angioplasty (univariate: 2.2% vs. 24.7%; P = 0.001; multivariate: OR = 0.46; P = 0.0230). In patients with AMI and contraindications for thrombolytic therapy, primary angioplasty was associated with a significantly lower mortality compared to conservative treatment. Therefore, hospitals without the facilities to perform primary angioplasty should try to refer such patients to centers with the facilities for such a service, if this is possible in an acceptable time.Cathet. Cardiovasc. Intervent. 46:127–133, 1999.

Emergent cardiac surgery during transcatheter aortic valve implantation (TAVI): a weighted meta-analysis of 9,251 patients from 46 studies.

AIMS Transcatheter aortic valve implantation (TAVI) is a novel treatment option for high surgical risk patients with severe symptomatic aortic valve (AV) stenosis. During TAVI, some patients may require emergent cardiac surgery (ECS). However, the incidence, reasons and outcomes of those needing ECS remain unknown. METHODS AND RESULTS We performed a search of the English medical literature using MEDLINE to identify all studies on TAVI and evaluate the incidence of ECS (i.e., within 24 hrs of TAVI) and outcomes for these patients. Forty-six studies comprising 9,251 patients undergoing transfemoral, transapical or trans-subclavian TAVI for native AV stenosis published between 01/2004 and 11/2011 were identified and included in this weighted meta-analysis. Overall, TAVI patients were old (mean=81.3±5.4 years) and had a high mean logistic EuroSCORE (24.4±5.9%). Few patients required ECS (n=102; 1.1±1.1%) and this was marginally higher among those undergoing transapical TAVI as compared to those undergoing transarterial TAVI (1.9±1.7% vs. 0.6±0.9%). Data on the reasons for ECS were available in 86% (88/102 patients) and 41% of these (36/88) were performed for embolisation/dislocation of the AV prosthesis, with aortic dissection (n=14), coronary obstruction (n=5), severe AV regurgitation (n=10), annular rupture (n=6), aortic injury (n=14), and myocardial injury including tamponade (n=12) constituting the rest. Mortality at 30 days was about 9-fold higher in patients who did need as compared with those patients who did not need ECS (67.1±37.9% vs. 7.5±4.0%). CONCLUSIONS Reported rates of ECS during TAVI were low with embolisation or dislocation of the prosthesis being the most common cause. ECS was associated with grave prognosis with two out of three patients dying by 30 days. Thus, refinement in TAVI technology should not only focus on miniaturisation and improving flexibility of the delivery systems and/or devices -which may have the potential for decreasing aortic dissection, annular rupture, and tamponade- but also incorporate modifications to prevent embolisation/dislocation of the valve.

Frühbehandlung des akuten Myokardinfarktes: Umsetzung von Therapierichtlinien in den klinischen Alltag, MITRA-Pilotphase

MITRA (Maximale Individuelle TheRapie beim Akuten Myokardinfarkt) ist eine Anwendungsbeobachtung für den stationären und poststationären Verlauf eines nicht selektierten Patientenkollektivs mit akutem transmuralem Infarkt. Es sollen die Praktikabilität, der optimale Einsatz und die Sicherheit einer „individuell optimierten” Infarkttherapie untersucht werden. Zusätzlich soll die Qualität der Infarkttherapie in bezug auf jeden einzelnen Therapiebaustein abgeschätzt werden. An der multizentrischen Studie beteiligen sich fast flächendeckend 54 Kliniken einer umschriebenen Region im Südwesten Deutschlands. In der Pilotphase wurden konsekutiv 1303 Patienten mit akutem transmuralem Infarkt eingeschlossen. Im Median betrug das Alter 66 Jahre, ⅔ waren Männer. Die Prähospitalzeit war 2,7 Stunden, 64% erreichten die Klinik innerhalb der ersten 4 Stunden nach Symptombeginn. Bei 47% bestand ein Vorderwandinfarkt. In den Subgruppen der Patienten, die keine absolute Kontraindikationen hatten, erhielten: 53,4% das Thrombolytikum, 87,6% ASS, 37,1% den Betablocker und 17,4% der Patienten den ACE-Hemmer. In einer gesonderten Betrachtung wurden Patienten als „optimal behandelt” definiert, wenn sie in der Akutphase Thrombolyse, ASS und Betablocker nur dann erhielten, wenn sie absolute Kontraindikationen hatten. Bekamen die Patienten mindestens eines dieser drei Therapeutika nicht, obwohl absolute Kontraindikationen nicht vorlagen, wurden sie als „suboptimal behandelt” klassifiziert. Nur 29% (n = 383) der Patienten wurden „optimal”, während 71% (n = 775) suboptimal behandelt wurden. Die univariate Analyse ergab, daß die optimal therapierten Patienten jünger waren, sie hatten häufiger ein eindeutiges EKG oder einen Linksschenkelblock, einen Vorderwandinfarkt, eine manifeste Herzinsuffizienz, AV-Block, Bradykardie oder eine fortgeschrittene COLD. Die Prähospitalzeit war häufiger verfügbar. Im optimal behandelten Kollektiv betrug die 48-h-Mortalität 5,0% vs. 9,3% im suboptimal behandelten Kollektiv und die Krankenhausmortalität 10,9% vs. 17,7%. Die multivariate Analyse zeigte, daß die Variable „optimale Therapie” ein unabhängiger Prädiktor sowohl für die Früh- als auch für die Krankenhausmortalität ist. Intrahospitale Komplikationen traten auf: Apoplex 2,8%, Reinfarkt 12,9%, Herzinsuffizienz 21,5%, kardiogener Schock 10,4% und Krankenhaussterblichkeit 18,1% (Letalität < 48 h 9,5%). Zwischen den Erkenntnissen und Empfehlungen aus großen randomisierten Therapiestudien und der klinischen Praxis besteht zum jetzigen Zeitpunkt eine deutliche Diskrepanz. Nach den vorliegenden Daten sollte die Qualität der derzeitigen medikamentösen Infarkttherapie noch deutlich verbessert werden, denn „optimale Therapie” ist ein günstiger Prädiktor für die Früh- und Klinikmortalität. The prognostic value of thrombolytics, aspirin, beta-blockers and ACE-inhibitors has been well documented in large clinical trials, but the application of these drugs in clinical practice is not known. MITRA is a multicenter study of 54 hospitals in a defined region in southwest Germany. The aim is to document actual clinical practice (pilot phase) and to establish an individually optimised prognostic therapy for acute myocardial infarction, considering only the absolute contraindications for each drug. In the pilot phase, 1303 consecutive patients with acute transmural myocardial infarction were enrolled. The median age was 66 years, the prehospital time was 2.7 hours. 47 % had an anterior infarction. In the subgroup of patients without absolute contraindications, only 53.4% were treated with thrombolytics, 87.6% with aspirin, 37.1% with beta-blocker, and 17.4% with ACE-inhibitor. Out of these, patients were classified as “optimally treated” if they received thrombolysis, aspirin as well as beta-blocker. Patients were also included if any of these medications was withheld in the presence of absolute contraindications. Treatment was defined suboptimal, if the patients did not receive any of these three medications despite the absence of absolute contraindications. Only 29% (n = 383) received an optimal postinfarction therapy and 71% (n = 775) a suboptimal treatment. The univariate analysis revealed 10 variables influencing optimal therapy. In this subgroup patients were younger, they more often had clear ECG-findings or left bundle branch block, an anterior infarction, acute cardiac failure, AV-block, bradycardia, recent trauma or surgery (less then 2 weeks) and a severe chronic obstructive lung disease. The prehospital time was more often available. Early mortality after 2 days was 5.0% versus 9.3% in the suboptimal treated patients (OR: 0.5, CI: 0.30–0.86) the total inhospital mortality was 10.9% in the optimal versus 17.7% in the suboptimal group (OR: 0.6, CI: 0.38–0.84). In a multivariate analysis the parameter “optimal treatment” was found to be an independent predictor of the early (OR = 0.4; CI: 0.20–0.69) and the inhospital mortality (OR = 0.4; CI: 0.25–0.64). The following in-hospital events occurred: stroke 2.8%, reinfarction 12.9%, cardiac failure 21.5%, cardiogenic shock 10.4% and in-hospital mortality 18.1% (2-days mortality 9.5%). Pharmacological therapy for acute myocardial infarction is inconsistent with the recommendations suggested in recent clinical trials and needs to be individually optimised. Optimal treatment is an independent predictor of early and inhospital mortality.

Quantification of shunt volumes in congenital heart diseases using a breath-hold MR phase contrast technique: comparison with oximetry

Aims: Comparison of breath-hold MR phase contrast technique in the estimation of cardiac shunt volumes with the invasive oximetric technique. Methods and Results: Seventeen patients with various cardiac shunts (10 ASD, 3 VSD, 1 PDA, 3 PFO) and five healthy volunteers were investigated using a 1.5 Tesla system. The mean flow velocity, the mean volume flow and the transverse area in the ascending aorta and the left and right pulmonary artery were measured using the MR phase contrast breath-hold technique (through plane, FLASH 2D-sequence, TR/TE 11/5 ms, phase length 106 ms, VENC 250 cm/s). The ratio of mean flow in the pulmonary (Qp: sum of mean flows in the left and right pulmonary arteries) and the systemic circulation (Qs: mean flow in the ascending aorta) was calculated and compared with invasively measured Qp:Qs ratios. Oximetry was performed within 24 h of the MR investigation. The non-invasive shunt measurement in the 17 patients showed a mean Qp:Qs ratio of 2.00 ± 0.86. Comparing the MR data with the invasively measured Qp:Qs showed a correlation coefficient of r = 0.91 (p < 0.001). Conclusion: Cardiac shunt volumes can be measured reliably using a shorter acquisition time with breath-hold MR phase contrast technique.

Outcomes of transfemoral transcatheter aortic valve implantation at hospitals with and without on-site cardiac surgery department: insights from the prospective German aortic valve replacement quality assurance registry (AQUA) in 17 919 patients

AIMS Performing transcatheter aortic valve implantation (TAVI) at hospitals with only cardiology department but no cardiac surgery (CS) on-site is at great odds with current Guidelines. METHODS AND RESULTS We analysed data from the official, prospective German Quality Assurance Registry on Aortic Valve Replacement to compare characteristics and in-hospital outcomes of patients undergoing transfemoral TAVI at hospitals with (n = 75) and without CS departments (n = 22). An interdisciplinary Heart Team was established at all centres (internal staff physicians at hospitals with on-site CS; in-house cardiologists and visiting cardiac surgical teams from collaborating hospitals at non-CS hospitals). In 2013 and 2014, 17 919 patients (81.2 ± 6.1 years, 55% females, German aortic valve (GAV) score 2.0 5.6 ± 5.8%, logistic EuroSCORE I 21.1 ± 15.4%) underwent transfemoral TAVI in Germany: 1332 (7.4%) at hospitals without on-site CS department. Patients in non-CS hospitals were older (82.1 ± 5.8 vs. 81.1 ± 6.1 years, P < 0.001), with more frequent co-morbidities. Predicted mortality risks per GAV-score 2.0 (6.1 + 5.5 vs. 5.5 ± 5.9%, P < 0.001) and logEuroSCORE I (23.2 ± 15.8 vs. 21.0 ± 15.4%, P < 0.001) were higher in patients at non-CS sites. Complications, including strokes (2.6 vs. 2.3%, P = 0.452) and in-hospital mortality (3.8 vs. 4.2%, P = 0.396), were similar in both groups. Matched-pair analysis of 555 patients in each group with identical GAV-score confirmed similar rates of intraprocedural complications (9.2 vs. 10.3%, P = 0.543), strokes (3.2% for both groups, P = 1.00), and in-hospital mortality (1.8 vs. 2.9%, P = 0.234). CONCLUSION Although patients undergoing TAVI at hospitals without on-site CS department were older and at higher predicted perioperative death risk, major complications, and in-hospital mortality were not statistically different, suggesting the feasibility and safety of Heart Team-based TAVI at non-CS sites. These findings need confirmation in future randomized study.

Acute myocardial infarction occurring in versus out of the hospital: patient characteristics and clinical outcome

OBJECTIVES We describe the baseline characteristics and clinical course of patients who had an acute myocardial infarction (AMI) during their hospital stay. BACKGROUND In comparison with patients who had an AMI outside of the hospital (prehospital AMI), the data on patients who had an AMI in the hospital are poorly described. METHODS Patients with an in-hospital AMI were prospectively registered in the Southwest German Maximal Individual TheRapy in Acute myocardial infarction (MITRA) study and compared with patients with prehospital AMI. RESULTS Of 5,888 patients with AMI, 403 patients (6.8%) had an in-hospital AMI. These patients were older, more often male and sicker as compared with the patients with a prehospital AMI. They also showed a higher prevalence of concomitant diseases, such as arterial hypertension, diabetes mellitus, renal insufficiency and contraindications for thrombolysis. There was no significant difference regarding the use of reperfusion therapy, either thrombolysis (in-hospital AMI 44.2% vs. prehospital AMI 49.1%; odds ratio [OR] 0.86, 95% confidence interval [CI] 0.70 to 1.05) or primary angioplasty (9.9% vs. 8.2%; OR 1.23, 95% CI 0.88 to 1.73), or a combination of both, between the two groups. The interval from symptom onset to the start of treatment in patients receiving reperfusion therapy was 55 min for patients with an in-hospital AMI versus 180 min for patients with a prehospital AMI (p = 0.001). In-hospital death occurred in 110 (27.3%) of 403 patients with an in-hospital versus 762 (13.9%) of 5,485 patients with a prehospital AMI (OR 2.33, 95% CI 1.85 to 2.94). This was confirmed by logistic regression analysis after adjusting for other confounding variables (OR 1.67, 95% CI 1.23 to 2.24). CONCLUSIONS In-hospital AMI occurred in 6.8% of patients. Time to intervention was shorter; however, the use of reperfusion therapy for in-hospital AMI was not different from that for prehospital AMI. In particular, primary angioplasty seems to be underused in these patients. This, as well as the selection of patients, may result in the high hospital mortality rate of 27.3%.