Discoveries in peripartum cardiomyopathy Fett, James D., MD, MPH; Markham, David W., MD
Trends in cardiovascular medicine,
07/2015, Letnik:
25, Številka:
5
Journal Article
Recenzirano
Abstract The past decade has seen remarkable gains for outcomes in peripartum cardiomyopathy (PPCM), one of the leading causes of maternal mortality and morbidity in the USA and many other countries, ...including the high-incidence areas of Haiti and South Africa. This review article emphasizes the importance of continuing the process of increasing awareness of PPCM and presents details of this evolving picture, including important discoveries that point the way to full recovery for almost all PPCM subjects. In addition, new interventions will be highlighted, which may facilitate recovery. Numerous studies have demonstrated that when the diagnosis of PPCM is made with LVEF > 0.30, the probability is that recovery to LVEF ≥ 0.50 will occur in the overwhelming majority of subjects. PPCM patients diagnosed with severely depressed systolic function (LVEF < 0.30) and a remodeled left ventricle with greater dilatation (LVEDd ≥ 60 mm) are least likely to reach the outcome recovery goals. These are the patients with the greatest need for newer interventional strategies.
Fulminant myocarditis Gupta, Sachin; Markham, David W; Drazner, Mark H ...
Nature clinical practice cardiovascular medicine,
11/2008, Letnik:
5, Številka:
11
Journal Article
Recenzirano
Fulminant myocarditis is an inflammatory process that occurs in the myocardium and causes acute-onset heart failure. If patients with fulminant myocarditis are aggressively supported in a timely ...manner, nearly all can have an excellent recovery. In this Review, we discuss the clinical and histological distinguishing features of fulminant myocarditis and contrast this disease entity with nonfulminant myocarditis. The epidemiology, pathophysiology, clinical presentation, methods of diagnosis, management options and prognosis of fulminant myocarditis are reviewed in detail.
Left ventricular assist devices (LVADs) are now widely accepted as an option for patients with advanced heart failure. First-generation devices were pulsatile, but they had poor longevity and ...durability. Newer generation devices are nonpulsatile and more durable, but remain associated with an increased risk of stroke and hypertension. Moreover, little is understood about the physiological effects of the chronic absence of pulsatile flow in humans.
We evaluated patients with pulsatile (n=6) and nonpulsatile (n=11) LVADs and healthy controls (n=9) during head-up tilt while measuring hemodynamics and muscle sympathetic nerve activity. Patients with nonpulsatile devices had markedly elevated supine and upright muscle sympathetic nerve activity (mean±SD, 43±15 supine and 60±21 bursts/min at 60° head-up tilt) compared with patients with pulsatile devices (24±7 and 35±8 bursts/min; P<0.01) and controls (11±6 and 31±6 bursts/min; P<0.01); however, muscle sympathetic nerve activity was not different between patients with pulsatile flow and controls (P=0.34). Heart rate, mean arterial pressure, and total peripheral resistance were greater, whereas cardiac output was smaller, in LVAD patients compared with controls in both supine and upright postures. However, these hemodynamic variables were not significantly different between patients with pulsatile and nonpulsatile flow.
Heart failure patients with continuous, nonpulsatile LVADs have marked sympathetic activation, which is likely due, at least in part, to baroreceptor unloading. We speculate that such chronic sympathetic activation may contribute to, or worsen end-organ diseases, and reduce the possibility of ventricular recovery. Strategies to provide some degree of arterial pulsatility, even in continuous flow LVADs may be necessary to achieve optimal outcomes in these patients.
Patients with muscular dystrophy are at risk of developing a dilated cardiomyopathy and can progress to advanced heart failure. At present, it is not known whether such patients can safely undergo ...cardiac transplantation.
This was a retrospective review of the Cardiac Transplant Research Database, a multi-institutional registry of 29 transplant centers in the United States, from the years 1990 to 2005. The post-cardiac transplant outcomes of 29 patients with muscular dystrophy were compared with 275 non-muscular dystrophy patients with non-ischemic cardiomyopathy, matched for age, body mass index, gender, and race.
Becker's muscular dystrophy was present in 52% of the patients. Survival in the muscular dystrophy patients was similar to the controls at 1 year (89% vs 91%; p = 0.5) and at 5 years (83% vs 78%; p = 0.5). The differences in rates of cumulative infection, rejection, or allograft vasculopathy between the 2 groups were not significant (p > 0.5 for all comparisons).
Recognizing the limitations of the present investigation (ie, selection bias and data lacking in the functional capacity of the muscular dystrophy patients), the current study suggests that the clinical outcomes after cardiac transplantation in selected patients with muscular dystrophy are similar to those seen in age-matched patients with non-ischemic cardiomyopathy.
Although right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) are correlated in heart failure, in a sizeable minority of patients, the RAP and PCWP are not tightly coupled. The ...basis of this variability in the RAP/PCWP ratio, and whether it conveys prognostic value, is not known.
We analyzed the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial database. Baseline characteristics, including echocardiographic assessment of right ventricular (RV) structure and function, and invasively measured hemodynamic parameters, were compared among tertiles of the RAP/PCWP ratio. Multivariable Cox proportional hazard models assessed the association of RAP/PCWP ratio with the primary ESCAPE outcome (6-month death or hospitalization days) adjusting for systolic blood pressure, blood urea nitrogen, 6-minute walk distance, and PCWP. The RAP/PCWP tertiles were 0.27 to 0.4 (tertile 1); 0.41 to 0.615 (tertile 2), and 0.62 to 1.21 (tertile 3). Increasing RAP/PCWP was associated with increasing median right atrial area (23, 26, 29 cm2, respectively; P<0.005), RV area in diastole (21, 27, 27 cm2, respectively; P<0.005), and pulmonary vascular resistance (2.4, 2.9, 3.6 woods units, respectively; P=0.003), and lower RV stroke work index (8.6, 8.4, 5.5 g·m/m2 per beat, respectively; P<0.001). RAP/PCWP ratio was associated with death or hospitalization within 6 months (hazard ratio, 1.16 1, 1.4; P<0.05).
Increased RAP/PCWP ratio was associated with higher pulmonary vascular resistance, reduced RV function (manifest as a larger right atrium and ventricle and lower RV stroke work index), and an increased risk of adverse outcomes in patients with advanced heart failure.
Whether concentric left ventricular (LV) hypertrophy (LVH) is a common precursor to depressed LV ejection fraction (EF) in humans is uncertain. From 1992 through 1994, 555 patients at our institution ...underwent echocardiography and had LVH (posterior or septal wall thickness ≥1.3 cm or concentric LVH noted) and normal LVEF. Of these, 220 (40%) had a follow-up assessment of LVEF by December 2008. The duration of follow-up was classified as short (≤7.5 years) or long (>7.5 years) term. The primary outcome was the development of a qualitatively depressed LVEF (mildly, moderately, or severely depressed). After a median follow-up of 7.5 years, 20% of the patients with concentric LVH developed a low LVEF. A low LVEF developed in 13% of subjects without interval myocardial infarction (MI) and 50% of subjects with interval MI during short-term follow-up (p <0.005). A low LVEF developed in 20% of subjects without interval MI and 44% of subjects with interval MI during long-term follow-up (p = 0.01). Of the subjects who developed a reduced LVEF, the relative wall thickness (median 0.5, 25th to 75th percentile 0.4 to 0.6) at follow-up was consistent with a concentric, rather than eccentric, phenotype. In conclusion, in patients with concentric LVH, the transition from a normal LVEF to a low LVEF was relatively infrequent (20%) after long-term follow-up in the absence of interval MI and usually did not result in a change in the LV geometry from a concentric to an eccentric phenotype.
The pathophysiology of peripartum cardiomyopathy (PPCM) and its distinctive biological features remain incompletely understood. High-throughput serum proteomic profiling, a powerful tool to gain ...insights into the pathophysiology of diseases at a systems biology level, has never been used to investigate PPCM relative to nonischemic cardiomyopathy.
To characterize the pathophysiology of PPCM through serum proteomic analysis.
Aptamer-based proteomic analysis (SomaScan 7K) was performed on serum samples from women with PPCM (n = 67), women with nonischemic nonperipartum cardiomyopathy (NPCM) (n = 31), and age-matched healthy peripartum and nonperipartum women (n = 10 each). Serum samples were obtained from the IPAC (Investigation of Pregnancy-Associated Cardiomyopathy) and IMAC2 (Intervention in Myocarditis and Acute Cardiomyopathy) studies.
Principal component analysis revealed unique clustering of each patient group (P for difference <0.001). Biological pathway analyses of differentially measured proteins in PPCM relative to NPCM, before and after normalization to pertinent healthy controls, highlighted specific dysregulation of inflammatory pathways in PPCM, including the upregulation of the cholesterol metabolism-related anti-inflammatory pathway liver-X receptor/retinoid-X receptor (LXR/RXR) (P < 0.01, Z-score 1.9-2.1). Cardiac recovery by 12 months in PPCM was associated with the downregulation of pro-inflammatory pathways and the upregulation of LXR/RXR, and an additional RXR-dependent pathway involved in the regulation of inflammation and metabolism, peroxisome proliferator-activated receptor α/RXRα signaling.
Serum proteomic profiling of PPCM relative to NPCM and healthy controls indicated that PPCM is a distinct disease entity characterized by the unique dysregulation of inflammation-related pathways and cholesterol metabolism-related anti-inflammatory pathways. These findings provide insight into the pathophysiology of PPCM and point to novel potential therapeutic targets.
Background Guidelines recommend that patients with new-onset systolic heart failure (HF) receive a trial of medical therapy before an implantable cardiac defibrillator (ICD). This strategy allows for ...improvement of left ventricular ejection fraction (LVEF), thereby avoiding an ICD, but exposes patients to risk of potentially preventable sudden cardiac death during the trial of medical therapy. Methods We reviewed a consecutive series of patients with HF of < 6 months duration with a severely depressed LVEF (< 30%) evaluated in a HF clinic (N = 224). The ICD implantation was delayed with plans to reassess LVEF approximately 6 months after optimization of β-blockers. Mortality was ascertained by the National Death Index. Results Follow-up echocardiograms were performed in 115 of the 224 subjects. Of these, 50 (43%) had mildly depressed or normal LVEF at follow-up (“LVEF recovery”) such that an ICD was no longer indicated. In a conservative sensitivity analysis (using the entire study cohort, whether or not a follow-up echocardiogram was obtained, as the denominator), 22% of subjects had LVEF recovery. Mortality at 6, 12, and 18 months in the entire cohort was 2.3%, 4.5%, and 6.8%, respectively. Of 87 patients who tolerated target doses of β-blockers, only 1 (1.1%) died during the first 18 months. Conclusion Patients with new-onset systolic HF have both a good chance of LVEF recovery and low 6-month mortality. Achievement of target β-blocker dose identifies a very low-risk population. These data support delaying ICD implantation for a trial of medical therapy.
Abstract Background Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. Objectives This study sought to prospectively evaluate recovery of the left ventricular ...ejection fraction (LVEF) and clinical outcomes in the multicenter IPAC (Investigations of Pregnancy Associated Cardiomyopathy) study. Methods We enrolled and followed 100 women with PPCM through 1 year post-partum. The LVEF was assessed by echocardiography at baseline and at 2, 6, and 12 months post-partum. Survival free from major cardiovascular events (death, transplantation, or left ventricular LV assist device) was determined. Predictors of outcome, particularly race, parameters of LV dysfunction (LVEF), and remodeling (left ventricular end-diastolic diameter LVEDD) at presentation, were assessed by univariate and multivariate analyses. Results The cohort was 30% black, 65% white, 5% other; the mean patient age was 30 ± 6 years; and 88% were receiving beta-blockers and 81% angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The LVEF at study entry was 0.35 ± 0.10, 0.51 ± 0.11 at 6 months, and 0.53 ± 0.10 at 12 months. By 1 year, 13% had experienced major events or had persistent severe cardiomyopathy with an LVEF <0.35, and 72% achieved an LVEF ≥0.50. An initial LVEF <0.30 (p = 0.001), an LVEDD ≥6.0 cm (p < 0.001), black race (p = 0.001), and presentation after 6 weeks post-partum (p = 0.02) were associated with a lower LVEF at 12 months. No subjects with both a baseline LVEF <0.30 and an LVEDD ≥6.0 cm recovered by 1 year post-partum, whereas 91% with both a baseline LVEF ≥0.30 and an LVEDD <6.0 cm recovered (p < 0.00001). Conclusions In a prospective cohort with PPCM, most women recovered; however, 13% had major events or persistent severe cardiomyopathy. Black women had more LV dysfunction at presentation and at 6 and 12 months post-partum. Severe LV dysfunction and greater remodeling at study entry were associated with less recovery. (Investigations of Pregnancy Associated Cardiomyopathy IPAC; NCT01085955 )
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