Roman Pfister

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy

BACKGROUND The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

Use of NT‐proBNP in routine testing and comparison to BNP

B‐type natriuretic peptide (BNP) is a strong diagnostic predictor of left‐ventricular (LV)‐dysfunction. Recently, the aminoterminal portion of pro‐BNP (NT‐proBNP) has been introduced, which could be even more sensitive because of its longer half‐life. The aim of this study was to evaluate the new marker NT‐proBNP within a large, heterogeneous population of patients with suspected cardiovascular disease at risk of cardiovascular dysfunction and to compare it with the established diagnostic parameter BNP.

Decreased number of circulating progenitor cells in obesity: beneficial effects of weight reduction

AIMS Cardiovascular risk factors are associated with decreased levels of circulating progenitor cells (CPC). The aim of this study was to determine whether the number of CPC is an independent correlate of body mass index (BMI) and whether weight loss leads to an increase in CPC. METHODS AND RESULTS CD34 positive and KDR/CD34, CD133/CD34, and CD117/CD34 double positive cells were measured by fluorescence activated cell sorting (FACS) analysis in peripheral blood of 149 volunteers (52.5 +/- 12.0 years, BMI 21.5-52.7 kg/m(2), mean 31.6 +/- 5.1 kg/m(2)) participating in a weight reduction program offered by German pharmacies. In addition, carotid intima media thickness (IMT) and brachial artery flow-mediated dilatation were determined. After a diet and sports program for 6 months, 86 representing subjects were re-evaluated (mean weight loss 5.8 +/- 5.2 kg). There was an inverse correlation between BMI as well as waist circumference and CPC, especially CD34 positive, KDR/CD34 positive, CD133/CD34 positive, and CD117/CD34 positive cells. This decrease in CPC in obesity held true not only for the absolute cell numbers, but also for the relative fractions of KDR, CD133, and CD117 positive cells within the CD34 positive cells, indicating a specific down regulation of these progenitor cell types. Multiple regression analysis revealed that BMI was a more prominent predictor of CPC regulation than blood pressure, LDL cholesterol, triglycerides, fasting glucose, and smoking. IMT increased in dependence on BMI (P < 0.001) and was inversely correlated with the number of CD34 positive cell (P < 0.05). After diet, there was a significant increase of CD34 and CD117/CD34 positive cells, which correlated with the decrease in BMI. Also, weight loss was accompanied by a decrease in IMT (P = 0.015), which also correlated with the increase in CPC (P < 0.001). The increase in the number of CPC was independent from whether weight loss was achieved by increased physical exercise or by reduced calorie intake only. CONCLUSION Obesity is associated with decreased numbers of CPC and increased IMT. Diet and weight loss lead to an increase in CPC count, which might contribute to regression of IMT.

Mild therapeutic hypothermia in cardiogenic shock syndrome.

Objective:Mortality in patients with cardiogenic shock after out-of-hospital cardiac arrest remains high despite advances in resuscitation and early revascularization strategies. Recent studies suggest a reduced mortality in survivors of cardiac arrest subjected to mild therapeutic hypothermia, but the underlying mechanisms are not yet clear. Because positive hemodynamic effects of mild therapeutic hypothermia have been suggested, we aimed at testing the hypothesis that patients in cardiogenic shock might benefit from mild therapeutic hypothermia. Methods:Hemodynamic effects of mild therapeutic hypothermia in 20 consecutive patients admitted in cardiogenic shock after successful resuscitation from out-of-hospital cardiac arrest were investigated. A historic normothermic control group was matched (one-to-one) by means of a propensity score. Patients were cooled to 33°C for 24 hrs using an endovascular cooling device and hemodynamic variables were continuously recorded by means of pulse contour analysis. Cardiac performance was determined by echocardiography. Results:Mild therapeutic hypothermia induced a significant decrease in heart rate from 74 to 64 beats per minute. Despite the reduction in heart rate, cardiac index remained unchanged under mild therapeutic hypothermia likely due to an increase in ejection fraction from 43 ± 4% to 55 ± 4%. Mean arterial pressure increased rapidly from 75 ± 2 mm Hg to 84 ± 3 mm Hg (p = .001) upon induction of hypothermia paralleled by an initial increase in systemic vascular resistance. Accordingly, patients with mild therapeutic hypothermia required lower cumulative doses of vasopressors and inotropes. Conclusions:We conclude that in cardiogenic shock mild therapeutic hypothermia provides circulatory support and an increase in systemic vascular resistance that leads to reduced vasopressor use and may result in lower oxygen consumption. These findings suggest that mild therapeutic hypothermia could be a therapeutic option in hemodynamically unstable patients independent of cardiac arrest and further randomized clinical studies are needed.

Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies.

Using mendelian randomization, Roman Pfister and colleagues demonstrate a potentially causal link between low levels of B-type natriuretic peptide (BNP), a hormone released by damaged hearts, and the development of type 2 diabetes.

Minimally invasive transapical aortic valve implantation and the risk of acute kidney injury.

BACKGROUND The new technique of minimally invasive transapical aortic valve implantation (TAP-AVI) deals with high-risk patients and despite the absence of cardiopulmonary bypass it might lead to renal impairment. The aim of this study was to estimate the risk of the development of acute kidney injury (AKI) after TAP-AVI and to identify possible risk factors with regard to the morbidity and mortality of the patients. METHODS Data of 30 consecutive patients undergoing TAP-AVI were recorded and followed up for 8 weeks. Postoperative AKI has been defined according to RIFLE criteria. Two patients on chronic hemodialysis have been followed up. RESULTS Of 28 patients, AKI occurred in 16 patients (57%). Statistical analysis revealed no influence on the risk of developing AKI caused by the dose of applicated contrast medium (p = 0.09), the patients age (p = 0.5), or the existence of diabetes (p = 0. 16). Analysis concerning the relationship between a preexisting coronary heart disease and AKI showed a tendency to be associated with a higher risk of the development of AKI (70% preexisting congenital heart disease in the AKI group versus 50%; p = 0.28). Only a preoperative serum creatinine greater than 1.1 mg/dL was a strong predictor for developing AKI (p < 0.01). Length of stay in the intensive care unit and the complete length of hospital stay revealed no difference with regard to postoperative development of AKI though statistical analysis showed a trend to a higher mortality in the AKI group (27% vs 6%); univariate analysis did not reach statistical significance (p = 0.13). CONCLUSIONS The TAP-AVI seems to be a feasible procedure for high-risk patients with a clear risk of developing AKI. Patients at risk should be identified and, if indicated, already preoperatively treated in collaboration with the attending nephrologists.

Prognostic impact of NT-proBNP and renal function in comparison to contemporary multi-marker risk scores in heart failure patients.

Multi‐marker risk scores accurately predict prognosis in heart failure patients but calculation is complex.

Estimated urinary sodium excretion and risk of heart failure in men and women in the EPIC-Norfolk study

Interventional trials provide evidence for a beneficial effect of reduced dietary sodium intake on blood pressure. The association of sodium intake with heart failure which is a long‐term complication of hypertension has not been examined.

Red cell distribution width is associated with physical inactivity and heart failure, independent of established risk factors, inflammation or iron metabolism; the EPIC—Norfolk study

AIMS Red cell distribution width (RDW) is associated with increased risk of heart failure (HF). We examined in a healthy population (1) whether this association is independent of cardiovascular risk factors and iron metabolism and (2) whether RDW associates with physical activity. METHODS AND RESULTS Hazard ratios (HRs, highest quartile versus lowest quartile of RDW) for the risk of HF were calculated in 17,533 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. During a follow-up of 11.2±2.2 years 640 participants developed a HF event. The HR for HF events was 1.44 (95%CI 1.15-1.80, p<0.001). There was a non-linear increase in HF risk across RDW quartiles. Adjustment for established risk factors (sex, age, diabetes, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol) attenuated the HR for HF to 1.40 (95%CI 1.11-1.77, p=0.001). Adjustment for CRP, iron and ferritin levels did not affect the HR for HF. RDW levels are inversely associated with physical activity (per category β=-0.37, 95%CI -0.053 to -0.021, p<0.0001), independent of iron metabolism. However, the association between HF and RDW levels was not changed by physical activity. CONCLUSIONS This study confirms that RDW is associated with HF events in an apparently healthy middle-aged population. More importantly, we show that the underlying pathophysiology linking HF with anisocytosis is not reflected by conventional risk factors, nor it is explained by iron metabolism or inflammation. Furthermore, RDW levels were associated with physical inactivity, but this did not influence the RDW-associated-risk of heart failure.

Bromocriptine for the treatment of peripartum cardiomyopathy: a multicentre randomized study

Abstract Aims An anti-angiogenic cleaved prolactin fragment is considered causal for peripartum cardiomyopathy (PPCM). Experimental and first clinical observations suggested beneficial effects of the prolactin release inhibitor bromocriptine in PPCM. Methods and results In this multicentre trial, 63 PPCM patients with left ventricular ejection fraction (LVEF) ≤35% were randomly assigned to short-term (1W: bromocriptine, 2.5 mg, 7 days) or long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for 6 weeks) in addition to standard heart failure therapy. Primary end point was LVEF change (delta) from baseline to 6 months assessed by magnetic resonance imaging. Bromocriptine was well tolerated. Left ventricular ejection fraction increased from 28 ± 10% to 49 ± 12% with a delta-LVEF of + 21 ± 11% in the 1W-group, and from 27 ± 10% to 51 ± 10% with a delta-LVEF of + 24 ± 11% in the 8W-group (delta-LVEF: P = 0.381). Full-recovery (LVEF ≥ 50%) was present in 52% of the 1W- and in 68% of the 8W-group with no differences in secondary end points between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6 months tended to be lower. No patient in the study needed heart transplantation, LV assist device or died. Conclusion Bromocriptine treatment was associated with high rate of full LV-recovery and low morbidity and mortality in PPCM patients compared with other PPCM cohorts not treated with bromocriptine. No significant differences were observed between 1W and 8W treatment suggesting that 1-week addition of bromocriptine to standard heart failure treatment is already beneficial with a trend for better full-recovery in the 8W group. Clinical trial registration ClinicalTrials.gov, study number: NCT00998556.