Gautam V. Ramani

Clinical Outcomes for Peripartum Cardiomyopathy in North America Results of the IPAC Study (Investigations of Pregnancy-Associated Cardiomyopathy)

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).

Chronic Heart Failure: Contemporary Diagnosis and Management

Chronic heart failure (CHF) remains the only cardiovascular disease with an increasing hospitalization burden and an ongoing drain on health care expenditures. The prevalence of CHF increases with advancing life span, with diastolic heart failure predominating in the elderly population. Primary prevention of coronary artery disease and risk factor management via aggressive blood pressure control are central in preventing new occurrences of left ventricular dysfunction. Optimal therapy for CHF involves identification and correction of potentially reversible precipitants, target-dose titration of medical therapy, and management of hospitalizations for decompensation. The etiological phenotype, absolute decrease in left ventricular ejection fraction and a widening of QRS duration on electrocardiography, is commonly used to identify patients at increased risk of progression of heart failure and sudden death who may benefit from prophylactic implantable cardioverter-defibrillator placement with or without cardiac resynchronization therapy. Patients who transition to advanced stages of disease despite optimal traditional medical and device therapy may be candidates for hemodynamically directed approaches such as a left ventricular assist device; in selected cases, listing for cardiac transplant may be warranted.

Safety and Efficacy of Bariatric Surgery in Morbidly Obese Patients with Severe Systolic Heart Failure

Morbid obesity (MO) is a risk factor for congestive heart failure (CHF). The presence of MO impairs functional status and disqualifies patients for cardiac transplantation. Bariatric surgery (BAS) is a frontline, durable treatment for MO; however, the safety and efficacy of BAS in advanced CHF is unknown.

Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension.

Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH). The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings.

Pulmonary Hypertension Affects Left Ventricular Basal Twist: A Novel Use for Speckle-Tracking Imaging

Background: Chronic pulmonary hypertension (PH) results in right ventricular (RV) mechanical dyssynchrony. However, its effects on left ventricular (LV) mechanics have not been examined. Objective: Since speckle‐tracking echocardiography (STE) is a novel approach to quantify LV dyssynchrony; we decided to use STE to assess the effect of PH on LV mechanics. Methods: Our echocardiography database was queried for patients with PH who had undergone STE analysis and compared to similarly collected data from a group of healthy volunteers. Results: Group I (15 patients, age of 53 ± 17 years, pulmonary artery pressure of 62 ± 20 mmHg, eccentricity index of 0.78 ± 0.06, and LV ejection fraction of 64 ± 11%) and Group II (8 healthy volunteers, age 41 ± 9 years, pulmonary artery pressure 14.6 ± 4.2 mmHg, eccentricity index of 1.02 ± 0.05, and LV ejection fraction of 66 ± 6 mmHg). There was no difference in QRS duration between the two groups. Although PH significantly altered basal LV twist (Group I: M =−5.76° versus Group II: M =−1.82°, P < 0.05), it had no effect on LV apical twist (5.29° versus 4.50°; P = NS, respectively). More notably, significant LV radial basal LV dyssynchrony, measured as the time to peak LV basal twist, was seen as a result of PH. Conclusions: STE identifies the presence of LV dyssynchrony in PH despite normal LV ejection fraction and no difference in QRS duration. Additional studies are now required to further characterize these results and determine their prognostic significance.

Veno-venous extracorporeal membrane oxygenation bridging to pharmacotherapy in pulmonary arterial hypertensive crisis

We report the case of a treatment-naive patient with pulmonary arterial hypertension who presented with decompensated right ventricular failure and cardiogenic shock. Unstable hemodynamics, hypoxia and end-organ hypoperfusion limited up-titration of pharmacotherapy. Mechanical circulatory support with veno-venous extracorporeal membrane oxygenation (VV-ECMO) was initiated to permit dose titration of pulmonary vasodilator therapy. VV-ECMO was weaned after 10 days of support, with successful transition to intravenous epoprostenol and oral sildenafil.

GNB3 C825T Polymorphism and Myocardial Recovery in Peripartum Cardiomyopathy Results of the Multicenter Investigations of Pregnancy-Associated Cardiomyopathy Study

Background—Black women are at greater risk for peripartum cardiomyopathy (PPCM). The guanine nucleotide–binding proteins &bgr;-3 subunit (GNB3) has a polymorphism C825T. The GNB3 TT genotype more prevalent in blacks is associated with poorer outcomes. We evaluated GNB3 genotype and myocardial recovery in PPCM. Methods and Results—A total of 97 women with PPCM were enrolled and genotyped for the GNB3 T/C polymorphism. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6 and 12 months postpartum. LVEF over time in subjects with the GNB3 TT genotype was compared with those with the C allele overall and in black and white subsets. The cohort was 30% black, age 30+6, LVEF 0.34+0.10 at entry 31+25 days postpartum. The % GNB3 genotype for TT/CT/CC=23/41/36 and differed markedly by race (blacks=52/38/10 versus whites=10/44/46, P<0.001). In subjects with the TT genotype, LVEF at entry was lower (TT=0.31+0.09; CT+CC=0.35+0.09, P=0.054) and this difference increased at 6 (TT=0.45+0.15; CT+CC=0.53+0.08, P=0.002) and 12 months (TT=0.45+0.15; CT+CC=0.56+0.07, P<0.001.). The difference in LVEF at 12 months by genotype was most pronounced in blacks (12 months LVEF for GNB3 TT=0.39+0.16; versus CT+CC=0.53+0.09, P=0.02) but evident in whites (TT=0.50++0.11; CT+CC=0.56+0.06, P=0.04). Conclusions—The GNB3 TT genotype was associated with lower LVEF at 6 and 12 months in women with PPCM, and this was particularly evident in blacks. Racial differences in the prevalence and impact of GNB3 TT may contribute to poorer outcomes in black women with PPCM.Background— Black women are at greater risk for peripartum cardiomyopathy (PPCM). The guanine nucleotide–binding proteins β-3 subunit (GNB3) has a polymorphism C825T. The GNB3 TT genotype more prevalent in blacks is associated with poorer outcomes. We evaluated GNB3 genotype and myocardial recovery in PPCM. Methods and Results— A total of 97 women with PPCM were enrolled and genotyped for the GNB3 T/C polymorphism. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6 and 12 months postpartum. LVEF over time in subjects with the GNB3 TT genotype was compared with those with the C allele overall and in black and white subsets. The cohort was 30% black, age 30+6, LVEF 0.34+0.10 at entry 31+25 days postpartum. The % GNB3 genotype for TT/CT/CC=23/41/36 and differed markedly by race (blacks=52/38/10 versus whites=10/44/46, P <0.001). In subjects with the TT genotype, LVEF at entry was lower (TT=0.31+0.09; CT+CC=0.35+0.09, P =0.054) and this difference increased at 6 (TT=0.45+0.15; CT+CC=0.53+0.08, P =0.002) and 12 months (TT=0.45+0.15; CT+CC=0.56+0.07, P <0.001.). The difference in LVEF at 12 months by genotype was most pronounced in blacks (12 months LVEF for GNB3 TT=0.39+0.16; versus CT+CC=0.53+0.09, P =0.02) but evident in whites (TT=0.50++0.11; CT+CC=0.56+0.06, P =0.04). Conclusions— The GNB3 TT genotype was associated with lower LVEF at 6 and 12 months in women with PPCM, and this was particularly evident in blacks. Racial differences in the prevalence and impact of GNB3 TT may contribute to poorer outcomes in black women with PPCM.

Assessment and management of cardiogenic shock in the emergency department.

Cardiogenic shock remains a major cause of morbidity and mortality in patients hospitalized with myocardial infarction, severe valvular disease, and other causes of cardiomyopathy. Emergency physicians play a pivotal role in the initial management of these patients, as they are most often the point of first contact with the medical system. This review discusses the initial assessment and management of cardiogenic shock, emphasizing the importance and role of the emergency physician.

Evaluación del riesgo en pacientes en estado crítico a la espera de trasplante: un paso adelante

Despite the advent of mechanical circulatory support, orthotopic heart transplantation (OHT) is still the long-term therapy of choice in selected patients with refractory heart failure. Most centers have experienced a change in ‘‘referral epidemiology’’ as increasingly sicker patients are being encountered with advanced heart failure symptoms refractory to inotropic therapy and with concomitant end-organ dysfunction. The reasons for this dramatic shift are elusive but are undoubtedly in part due to the lack of recognition among general clinicians that symptom control does not often translate into improved long-term prognosis in the contemporary cohort of late-stage heart failure patients. Importantly, the long endorsed classification of functional capacity using the New York Heart Association system is no longer optimal since pharmacological and device-based therapy have broadened the phenotypic presentation of late-stage heart failure. Clinicians now face a spectrum of phenotypes within the ‘‘advanced heart failure’’ group ranging from cardiogenic shock to impending shock, inotropic dependency with end-organ failure to intropic dependency without end-organ dysfunction, intermittently stable symptomatic states with recurrent and frequent decompensation, or chronic persistent symptoms resulting in substantial morbidity. The INTERMACS scale was a clinical attempt to further refine and stratify these myriad presentations of patients with late-stage heart failure undergoing left ventricular assist device (LVAD) implantation. The primary intent of this endeavor was to help stratify the appropriate population most likely to benefit from LVAD therapy but also to allow the community of clinicians to develop a communication strategy to convey disease severity. Using a linear scale from 1-7, the INTERMACS scale differentiates patients in a stepwise fashion from the sickest patients with shock (1) and organ hypoperfusion, requiring inotropic therapy, percutaneous mechanical circulatory support, and invasive hemodynamic monitoring, to those patients who suffer significant morbidity but maintain the ability to function adequately at home (7). This clinically useful scale was never subjected to validation of its prognostic accuracy, until recently. Not surprisingly, sicker patients with a lower INTERMACS score have increased mortality following LVAD implantation. Similarly objective, quantitative criteria have not been applied to patients undergoing primary heart transplantation. This is not to say that heart failure survival scores do not abound. In fact, there are several validated inpatient prognostic heart failure scoring systems, but these are not fully reflective of the entire spectrum of phenotypic presentation since they typically exclude the more critically ill INTERMACS 1-2 patients. In the article published in Revista Española de Cardiologı́a, BargeCaballero et al. sought to determine the usefulness of the INTERMACS scale in predicting outcomes for patients undergoing ‘‘urgent’’ transplantation. While ‘‘urgent’’ transplantation is not fully defined, the transplant times averaging 3 days imply consistency with the United States United Network for Organ Sharing status 1A listing, a category assigned to the sickest of patients. The rather short waiting times are once again a testimony to the success of the well admired ‘‘Spanish donation model’’. The investigators retrospectively analyzed nearly 2 decades of patient encounters with OHT from a single Spanish center between 19912009, and included all patients, including those on percutaneous or extracorporeal mechanical circulatory support. Notwithstanding the alterations in medical and percutaneous device therapy over these years, the authors independently adjudicated these patients into distinct categories of INTERMACS 1, INTERMACS 2, and INTERMACS 3/4 (combined into a third cohort of patients). The classification of patients appears accurate: INTERMACS 1 patients had an increased incidence of preoperative infections and hepato-renal dysfunction. As expected, the patients with theworse INTERMACS scores had poorer survival, with increased perioperative complications, including primary graft failure and renal failure. Survival curves dropped rapidly early and then plateaued, suggesting that the biggest obstacle in the patients classified as INTERMACS 1was getting through the early perioperative phase of transplantation. What can we learn from the current study? In addition to pointing to the validity of the INTERMACS scale in yet another clinical therapeutic scenario, the study quantifies what clinicians have known and practiced for several years: that patients must be Rev Esp Cardiol. 2011;64(3):175–176

Unraveling the paradox of cardiac tamponade: case presentation and discussion of physiology

A 53-year-old man on warfarin for postoperative pulmonary embolism presented with chest pain and was found to be in cardiac tamponade due to an atraumatic haemopericardium. Findings of tamponade and a novel approach to the pathophysiology of pericardial disease to explain these finding are presented.