Dominik Berliner

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.

BACKGROUND: Dyspnea is a common symptom affecting as many as 25% of patients seen in the ambulatory setting. It can arise from many different underlying conditions and is sometimes a manifestation of a life-threatening disease. METHODS: This review is based on pertinent articles retrieved by a selective search in PubMed, and on pertinent guidelines. RESULTS: The term dyspnea refers to a wide variety of subjective perceptions, some of which can be influenced by the patient's emotional state. A distinction is drawn between dyspnea of acute onset and chronic dyspnea: the latter, by definition, has been present for more than four weeks. The history, physical examination, and observation of the patient's breathing pattern often lead to the correct diagnosis, yet, in 30-50% of cases, more diagnostic studies are needed, including biomarker measurements and other ancillary tests. The diagnosis can be more difficult to establish when more than one underlying disease is present simultaneously. The causes of dyspnea include cardiac and pulmonary disease (congestive heart failure, acute coronary syndrome; pneumonia, chronic obstructive pulmonary disease) and many other conditions (anemia, mental disorders). CONCLUSION: The many causes of dyspnea make it a diagnostic challenge. Its rapid evaluation and diagnosis are crucial for reducing mortality and the burden of disease.

AIMS: Subsequent pregnancies (SSPs) in patients with peripartum cardiomyopathy (PPCM) have a high risk of heart failure relapse. We report on outcome of SSPs in PPCM patients in Germany, Scotland, and South Africa. METHODS AND RESULTS: Among 34 PPCM patients with a SSP, pregnancy ended prematurely in four patients while it was full-term in 30. Overall relapse rate [left ventricular ejection fraction, (LVEF) <50% or death after at least 6-month follow-up] was 56% with 12% (4/34) mortality. Relapse of PPCM after SSP was not associated with differences in parity, twin pregnancy, gestational hypertension, or smoking. Persistently reduced LVEF (<50%) before entering SSP was present in 47% of patients while full recovery (LVEF ≥50%) was present in 53%. The majority of patients entering SSP with persistently reduced LVEF were of African ethnicity (75%). Persistently reduced LVEF before SSP was associated with higher mortality (25% vs. 0%) and lower rate of full recovery at follow-up. Patients obtaining standard therapy for heart failure and bromocriptine immediately after delivery displayed significantly better LVEF at follow-up and a higher rate of full recovery with no patient dying compared with patients obtaining standard therapy for heart failure alone. This was independent of African or Caucasian race. CONCLUSION: Full recovery of LVEF before SSP was associated with lower mortality and better cardiac function at follow-up. Addition of bromocriptine to standard therapy for heart failure immediately after delivery was safe and seemed to be associated with a better outcome of SSP in African and Caucasian patients.

BACKGROUND: Heart failure (HF) pharmacotherapy is often not prescribed according to guidelines. This longitudinal study investigated prescription rates and dosages of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB), beta-blockers, and mineralocorticoid receptor antagonists (MRA), and concomitant changes of symptoms, echocardiographic parameters of left ventricular (LV) function and morphology and results of the Short Form-36 (SF-36) Health Survey in participants of the Interdisciplinary Network Heart Failure (INH) programme. METHODS AND RESULTS: The INH study evaluated a nurse-coordinated management, HeartNetCare-HF(TM) (HNC), against Usual Care (UC) in patients hospitalized for decompensated HF [LV ejection fraction (LVEF) ≤40% before discharge). A total of 706 subjects surviving >18 months (363 UC, 343 HNC) were examined 6-monthly. At baseline, 92% received ACEi/ARB, (HNC/UC 91/93%, P = 0.28), 86% received beta-blockers (86/86%, P = 0.83), and 44% received MRA (42/47%, P = 0.07). After 18 months, beta-blocker use had increased only in HNC (+7.6%, P < 0.001). Guideline-recommended target doses were achieved more frequently in HNC for ACEi/ARB (HNC/UC: 50/25%, P < 0.001) and beta-blockers (39/15%, P < 0.001). The following variables were more improved and/or better in subjects undergoing HNC compared with UC: LVEF (47 ± 12 vs. 44 ± 12%, P = 0.004, change +17/+14%, P = 0.010), LV end-diastolic diameter (59 ± 9 vs. 61 ± 9.6 mm, P = 0.024, change -2.3/-1.4 mm, P = 0.13), New York Heart Association class (1.9 ± 0.7 vs. 2.1 ± 0.7, P = 0.001, change -0.44/-0.25, P = 0.002) and SF-36 physical component summary score (41.6 ± 11.2 vs. 38.5 ± 11.8, P = 0.004, change +3.3 vs. +1.1 score points, P < 0.02). CONCLUSIONS: Prescription rates and dosages of ACEi/ARB and beta-blockers improved more in HNC than UC patients. Concomitantly, participation in HNC was associated with significantly better clinical outcomes and more favourable echocardiographic changes after 18 months.