Sergio Perrone

I Latin American Guidelines for the assessment and management of decompensated heart failure

Edimar Alcides Bocchi, Fabio Vilas-Boas, Sergio Perrone, Angel G Caamano, Nadine Clausell, Maria da Consolacao VMoreira, Jorge Thierer, Hugo Omar Grancelli, Carlos Vicente Serrano Junior, Denilson Albuquerque, Dirceu Almeida,Fernando Bacal, Luis Felipe Moreira, Adonay Mendonza, Antonio Magana, Arturo Tejeda, Daniel Chafes, Efraim Gomez,Erick Bogantes, Estela Azeka, Evandro Tinoco Mesquita, Francisco Jose Farias B Reis, Hector Mora, Humberto Vilacorta,Jesus Sanches, Joao David de Souza Neto, Jose Luis Vuksovic, Juan Paes Moreno, Julio Aspe y Rosas, Lidia ZytynskiMoura, Luis Antonio de Almeida Campos, Luis Eduardo Rohde, Marcos Parioma Javier, Martin Garrido Garduno, MucioTavares, Pablo Castro Galvez, Raul Spinoza, Reynaldo Castro de Miranda, Ricardo Mourilhe Rocha, Roberto Paganini,Rodolfo Castano Guerra, Salvador Rassi, Sofia Lagudis, Solange Bordignon, Solon Navarette, Waldo Fernandes, AntonioCarlos Pereira Barretto, Victor Issa, Jorge Ilha Guimaraes.

Heart Rate Is a Marker of Amiodarone Mortality Reduction in Severe Heart Failure

OBJECTIVES The impact of amiodarone on mortality in patients with severe congestive heart failure (CHF) (New York Heart Association functional classes II [advanced], III and IV; left ventricular ejection fraction < 35%) In the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA) trial was analyzed in relation to initial mean baseline heart rate (BHR) and its change after 6 months of follow-up. BACKGROUND Trials of amiodarone therapy in CHF have produced discordant results, suggesting that the effect is not uniform in all patient subgroups with regard to survival. METHODS The present analysis was carried out in 516 patients randomized to receive amiodarone, 300 mg/day (n = 260), or nonantiarrhythmic therapy (n = 256, control group) and followed up for 2 years. Survival was evaluated for patients with a BHR > or = 90 beats/min (control: n = 132; amiodarone: n = 122) and < 90 beats/min (control: n = 124; amiodarone: n = 138). Survival was also analyzed according to heart rate reduction at 6 months for 367 patients. RESULTS For patients with a BHR > or = 90 beats/min, amiodarone therapy reduced mortality to 38.4% compared with 62.4% in control patients (relative risk [RR] 0.55, 95% confidence interval [CI] 0.35 to 0.95, p < 0.002). Both sudden death (RR 0.46, 95% CI 0.24 to 0.90, p < 0.02) and progressive heart failure death (RR 0.60, 95% CI 0.30 to 1.03, p < 0.06) were reduced, and functional capacity was improved. In patients with a BHR < 90 beats/min, amiodarone did not alter survival. Among 367 patients who completed 6 months of follow-up, amiodarone reduced 2-year mortality only in those with a BHR > or = 90 beats/min, which was reduced at 6 months. CONCLUSIONS Elevated rest heart rates in severe CHF identify a subgroup of patients who benefit from treatment with amiodarone. Amiodarone-induced heart rate slowing may be an important benefit for patients.

Successful pregnancy and vaginal delivery after heart transplantation

Successful pregnancy and delivery in women with serious cardiovascular diseases have been reported. We describe here a patient with a transplanted heart, treated with cyclosporine and prednisone, who underwent pregnancy and vaginal delivery with good outcomes for mother and infant.

Pharmacotherapeutic approaches for decompensated heart failure: a role for the calcium sensitiser, levosimendan?

Although no universal definition exists, decompensated heart failure may be regarded as either a worsening of chronic heart failure or new‐onset heart failure precipitated by an acute incident. Haemodynamic management of patients hospitalised with decompensated heart failure may include the administration of diuretics, vasodilators and positive inotropic agents. Until recently, these latter agents constituted the only drug class to produce a direct increase in stroke volume via enhanced myocardial contractility. However, despite their short‐term benefits, the clinical utility of inotropic agents is compromised by their potentially deleterious effects on calcium handling and oxygen consumption, resulting in an increased risk of serious ventricular arrhythmias and death. In contrast, calcium sensitisers enhance cardiac performance without affecting calcium movement and, therefore, are potentially associated with a reduced risk of rhythmic disturbances. These agents constitute a heterogeneous group of compounds with different affinities for calcium sensitisation. Levosimendan is a potent calcium sensitiser with vasodilating properties that has been shown to provide symptomatic and haemodynamic improvement with no increase in oxygen consumption. Calcium sensitisation is therefore emerging as a promising treatment approach in this challenging therapeutic area.

International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure (REPORT-HF): Rationale for and design of a global registry

The clinical characteristics, initial presentation, management, and outcomes of patients hospitalized with new‐onset (first diagnosis) heart failure (HF) or decompensation of chronic HF are poorly understood worldwide. REPORT‐HF (International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) is a global, prospective, and observational study designed to characterize patient trajectories longitudinally during and following an index hospitalization for HF.

Amrinone stimulation test: Ability to predict improvement in left ventricular ejection fraction after coronary bypass surgery in patients with poor baseline left ventricular function

OBJECTIVES This study sought to determine whether the response to amrinone in patients with severe baseline left ventricular dysfunction can predict improvement in left ventricular ejection fraction after coronary artery bypass graft surgery. BACKGROUND Previous studies have suggested that the inotropic response to dobutamine can identify viable myocardium in the setting of chronic coronary disease and left ventricular dysfunction. However, increased oxygen demand stimulated by dobutamine can lead to superimposition of ischemia on the hibernating state, potentially confounding interpretation of results. Amrinone is an inotropic agent that does not critically augment myocardial oxygen demand and may be useful for identification of hibernating myocardium in the chronically ischemic state. METHODS Forty-four consecutive patients with coronary artery disease and left ventricular ejection fraction < 40% referred for coronary artery bypass graft surgery underwent amrinone stimulation (1 mg/kg body weight). Left ventricular ejection fraction was determined before amrinone stimulation, 20 min after infusion and 21 days after bypass surgery. RESULTS Baseline ejection fraction was 28 +/- 7% (mean +/- SD). Ejection fraction increased to 35 +/- 5% after amrinone stimulation (p < 0.0001) and to 33 +/- 6% after bypass surgery (p < 0.0001). Postbypass ejection fraction was significantly correlated with postamrinone ejection fraction (r = 0.65, p < 0.0001). Furthermore, the change in ejection fraction from baseline to after bypass surgery was highly correlated with the change in ejection fraction after amrinone stimulation (r = 0.75, p < 0.0001). Of 13 patients with an increase in ejection fraction > or = 10% after amrinone, all 13 had an increase of at least 8% and 11 (85%) of 13 had an increase > or = 10% after bypass surgery. In contrast, of 31 patients with an increase in ejection fraction < 10% after amrinone, only 2 (6%) had an increase > or = 10% (p < 0.0001) and 28 (90%) of 31 had an increase < 5% after bypass surgery. CONCLUSIONS Augmentation of myocardial contraction by amrinone in patients with chronic coronary artery disease and severe baseline left ventricular dysfunction predicts improvement in left ventricular ejection fraction after coronary artery bypass graft surgery.

Everolimus in de novo cardiac transplant recipients: 24-month follow-up

Purpose: A 24-month analysis of an international, double-blind trial comparing the safety and efficacy of everolimus (RAD, Certican™), a novel proliferation inhibitor under development that targets primary causes of chronic rejection, vs AZA in de novo heart transplant recipients. Methods: Patients (N=634) were randomised to either RAD 1.5 mg/day (N=209), RAD 3 mg/day (N=211) or AZA 1–3 mg/kg/day (N=214), with cyclosporin microemulsion, steroids and statins. The incidence of efficacy failure (acute rejection (ARJ) ≥3A, ARJ with HDC, graft loss, death or lost to follow-up) was determined. Incidence of allograft vasculopathy was assessed by IVUS. Results: Efficacy failure was significantly lower in the RAD 1.5 mg (p=0.016) and 3 mg (p<0.001) groups vs AZA (incidence: 45.9%, 36% and 57.5%, resp.). The incidence of ARJ was also significantly lower with RAD (1.5 mg: 34.9%, 3 mg: 22.7%, AZA: 48.1%). Patient survival was similar (90%, 86.3% and 88.8%). Viral infections occurred less frequently in both RAD groups, and CMV infection rates were significantly lower (8.6%, 8.1%) than in the AZA group (22.4%). The incidence of bacterial infections was higher with 3 mg RAD (40.3%) vs AZA (25.7%, p<0.05) and with 1.5 mg RAD (37.3%, p<0.05). Mean serum creatinine was higher in the RAD groups (p<0.001). Serum lipids (triglycerides, cholesterol, but not LDL and HDL) were elevated in RAD treated patients (p<0.05). The incidence of allograft vasculopathy determined by IVUS is being analysed and will also be presented. Conclusion: Both doses of RAD demonstrated superior efficacy compared to AZA by decreasing the incidence of ARJ as well as the composite endpoint. Overall safety and survival rate were better with 1.5 mg RAD compared to 3 mg.

Baseline Characteristics of Patients With Heart Failure and Preserved Ejection Fraction in the PARAGON-HF Trial

Background: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. Methods and Results: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), &bgr;-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464–1610), and structural heart disease. Conclusions: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.