Prognosis of patients with previous myocardial infarction, coronary slow flow, and normal coronary angiogram.

BACKGROUND: There is a common assumption that patients with coronary slow flow (CSF) have an excellent prognosis in the absence of coronary artery stenoses. Little is known about whether a history of previous coronary events affects the long-term survival in this population. In this retrospective, observational study, we assessed the possible association of a previous coronary event and long-term prognosis in patients with CSF but without significant coronary artery stenoses. METHODS: A total of 141 patients (70 male; median age: 59 years, range: 33-78 years) with CSF and normal coronary angiograms were included in the study. Patients were followed up for all-cause mortality during a period of 47 ± 22 months. RESULTS: Previous myocardial infarction (MI) was reported by 16 (11%) patients who had similar left ventricular ejection fraction (LVEF) as those without previous MI (51 ± 16 vs. 53 ± 16%, p = 0.595). Patients with previous MI more often had an abnormal resting electrocardiogram (69 vs. 40%, p = 0.03), while there were no significant differences in other baseline clinical characteristics (p > 0.05 for age, gender, risk factors, pharmacological treatment). In univariate Cox analysis, only previous MI was associated with unfavorable long-term survival (log-rank p = 0.012), while an abnormal electrocardiogram, LVEF, and other clinical variables were not (log-rank p > 0.05, for all). Kaplan-Meier analysis revealed unfavorable long-term survival in patients with CSF and a history of previous MI. CONCLUSION: In patients with CSF and an otherwise normal coronary angiogram, a history of a previous MI is associated with unfavorable long-term outcomes.

Secondary hyperparathyroidism prevalence and prognostic role in elderly males with heart failure.

AIM: Evaluation of secondary hyperparathyroidism (SHPT) and its prognostic impact on all-cause mortality in elderly males with heart failure (HF). METHODS: Seventy three males (67 ± 7 years old) with systolic HF were included. Baseline PTH was measured. Patients were grouped according to PTH cut-off levels of 65 pg/ml (>65 pg/ml = SHPT vs. normal PTH). All-cause mortality was evaluated at 6-year follow-up. RESULTS: SHPT was diagnosed in 43 (59 %) patients. They were more severe compared to the patients with normal PTH regarding NYHA functional class (2.4 ± 0.5 vs. 2.1 ± 0.2, p = 0.001), quality of life score (34 ± 14 vs. 24 ± 12, p = 0.005), 6-min walking distance (378 ± 79 vs. 446 ± 73 m, p < 0.0001), left ventricular ejection fraction (27 ± 8 vs. 31 ± 7 %, p = 0.019), and NT-proBNP [2452 (3399) vs. 918 (1372) pg/ml, p < 0.0001]. No differences in age, vitamin D status, and renal function were noted between studied groups. A total of 41 (56 %) patients died within 6 years of follow-up. Kaplan-Meier survival analysis showed impaired long-term survival in patients with SHPT versus patients with normal PTH (p = 0.009). The rate of death was highest (75 %) in the group of patients with SHPT and NT-proBNP levels above median value (p = 0.003). Cox regression analysis demonstrated that NT-proBNP was the single independent predictor of all-cause mortality at 6-year follow-up [HR 3.698 (1.927-7.095), p < 0.0001]. CONCLUSION: SHPT was highly prevalent in elderly males with HF and was associated with impaired survival. HF patients with SHPT had more severe disease compared to the patients with normal serum PTH. Determination of serum PTH levels provided additional value to NT-proBNP for risk stratification in these patients.

Efficacy and safety of the dual L- and T-type calcium channel blocker, ACT-280778: a proof-of-concept study in patients with mild-to-moderate essential hypertension.

ACT-280778 is an oral, non-dihydropyridine, dual L-/T-type calcium channel blocker. This phase 2a, double-blind, randomized, placebo- and active-controlled study investigated the efficacy and safety of 10 mg ACT-280778. Patients with mild-to-moderate essential hypertension received once-daily placebo (n=53), ACT-280778 10 mg (n=52) or amlodipine 10 mg (n=54) for 4 weeks. The primary end point was the change from baseline to week 4 in placebo-adjusted mean trough sitting diastolic blood pressure (SiDBP) with ACT-280778. Tolerability was assessed by recording treatment-emergent adverse events (TEAEs). Baseline clinical characteristics were similar across groups. No significant difference was observed at week 4 in mean trough SiDBP between placebo (-9.9 (95% confidence limit (CL) -12.7, -7.0) mm Hg) and ACT-280778 (-9.5 (-12.4, -6.5) mm Hg; P=0.86); amlodipine reduced mean trough SiDBP by -16.8 (-19.0, -14.5) mm Hg, confirming assay validity. Change in mean PR interval at week 4 (pre-dose) differed between placebo (-1.0 (95% CL -4.4, 2.3) ms) and ACT-280778 (6.5 (3.5, 9.6) ms); amlodipine did not increase PR interval (1.1 (-1.6, 3.9) ms).Treatment-emergent adverse events (TEAE) frequency was 32.1% (placebo), 32.7% (ACT-280778) and 33.3% (amlodipine). The most common TEAEs were headache, peripheral edema, hypertension and second-degree atrioventricular block. ACT-280778 (10 mg) did not lower blood pressure in mild-to-moderate hypertension.

Upright T wave in precordial lead V1 indicates the presence of significant coronary artery disease in patients undergoing coronary angiography with otherwise unremarkable electrocardiogram.

OBJECTIVE: The goal of the current work was to assess the possible relationship between upright T wave in precordial lead V1 (TV1) and the occurrence of coronary artery disease (CAD) in patients undergoing coronary angiography with an otherwise unremarkable resting electrocardiogram (ECG). METHODS: Twelve-lead resting ECGs of 2,468 patients who underwent coronary angiography were analyzed by independent reviewers blinded to the patients' clinical data. Patients with any condition known to affect cardiac repolarization were not eligible for inclusion. RESULTS: Of 126 patients included in the study, 76 (60%) had at least one significant coronary artery stenosis. Significant CAD was more frequently found in patients with upright TV1 as compared to those with negative TV1 (74 vs. 43%, p = 0.001). Left circumflex (LCx) and left anterior descending (LAD) coronary artery lesions were more frequently observed in patients with upright TV1 than in those with inverted TV1. In univariate analysis, patients with upright TV1 were approx 4 times more likely to have significant CAD than those with inverted TV1 (odds ratio (OR) 3.7, 95% confidence interval (CI) 1.744-7.897). In addition, in the multivariate logistic regression model, upright TV1 was an independent predictor of significant CAD (OR 4.249, 95% CI 1.594-11.328), along with previous myocardial infarction (OR 17.533, 95% CI 3.338-92.091), male gender (OR 3.020; 95% CI 1.214-7.510), and age (OR 1.061; 95% CI 1.003-1.122). CONCLUSION: It might be worthwhile to routinely evaluate the polarity of the T wave in lead V1 in patients with suspected CAD, since it appears to have additional risk stratification potential.

Association of increased parathyroid hormone with neuroendocrine activation and endothelial dysfunction in elderly men with heart failure.

High PTH levels have been reported in patients with chronic heart failure (CHF). Similarly, its levels increase with aging and are related to impaired survival in elderly adults. However, its relationship with neuroendocrine activation and endothelial dysfunction in CHF has not been previously studied. Seventy-three CHF males with New York Heart Association (NYHA) classes II and III and 20 control subjects aged ≥ 55 yr were recruited. PTH, 25-hydroxyvitamin D [25(OH)D], N-terminal pro-brain natriuretic peptide (NT-pro-BNP), adiponectin, and osteoprotegerin were measured. Endothelial function (brachial flow mediated dilation), echocardiography, physical performance, and quality of life were assessed, as well. CHF patients had markedly increased serum PTH (77 ± 33 vs 40 ± 11 pg/ml, p<0.0001), NT-pro-BNP [1809 (2742) vs 67 (74) pg/ml, p<0.0001], adiponectin (17 ± 9 vs 10 ± 2 µg/ml, p<0.0001), osteoprotegerin, whereas 25(OH)D levels were decreased compared to controls. Increased PTH is positively correlated with NTpro- BNP (r=0.399, p<0.0001), adiponectin (r=0.398, p<0.0001), and osteoprotegerin, whereas negatively with 25(OH)D in CHF patients. Additionally, increased serum PTH was associated with endothelial dysfunction, echocardiographic variables of heart failure progression, impaired physical performance, and deteriorated quality of life. In a multivariate linear regression analysis, increased serum PTH was independently associated with neuroendocrine activation (NT-pro-BNP, adiponectin) and endothelial dysfunction in elderly CHF men (R2=0.455). Additionally, demonstrated relations with other well-established variables of heart failure severity suggest the potential role of serum PTH in the pathogenesis and non-invasive monitoring of heart failure progression. Future studies are needed to evaluate the predictive value of serum PTH for clinical outcomes as well as beneficial potential of PTH suppression in CHF patients.

Ryanodine receptors, voltage-gated calcium channels and their relationship with protein kinase A in the myocardium.

We present a review about the relationship between ryanodine receptors and voltage-gated calcium channels in myocardium, and also how both of them are related to protein kinase A. Ryanodine receptors, which have three subtypes (RyR1-3), are located on the membrane of sarcoplasmic reticulum. Different subtypes of voltage-gated calcium channels interact with ryanodine receptors in skeletal and cardiac muscle tissue. The mechanism of excitation-contraction coupling is therefore different in the skeletal and cardiac muscle. However, in both tissues ryanodine receptors and voltage-gated calcium channels seem to be physically connected. FK-506 binding proteins (FKBPs) are bound to ryanodine receptors, thus allowing their concerted activity, called coupled gating. The activity of both ryanodine receptors and voltage-gated calcium channels is positively regulated by protein kinase A. These effects are, therefore, components of the mechanism of sympathetic stimulation of myocytes. The specificity of this enzyme's targeting is achieved by using different A kinase adapting proteins. Different diseases are related to inborn or acquired changes in ryanodine receptor activity in cardiac myocytes. Mutations in the cardiac ryanodine receptor gene can cause catecholamine-provoked ventricular tachycardia. Changes in phosphorylation state of ryanodine receptors can provide a credible explanation for the development of heart failure. The restoration of their normal level of phosphorylation could explain the positive effect of beta-blockers in the treatment of this disease. In conclusion, molecular interactions of ryanodine receptors and voltage-gated calcium channels with PKA have a significant physiological role. However, their defects and alterations can result in serious disturbances.

Preinfarction angina prevents left ventricular remodeling in patients treated with thrombolysis for myocardial infarction.

BACKGROUND: It has been shown that preinfarction angina may have beneficial effects on infarct size and mortality. However, there are no studies that have serially assessed the impact of preinfarction angina on left ventricular (LV) function in a large series of patients. HYPOTHESIS: The study was undertaken to determine whether preinfarction angina (within 7 days before infarction) influences LV remodeling. METHODS: In all, 119 consecutive patients with acute myocardial infarction were serially evaluated by 2-dimensional echocardiography (on Days 1, 2, 3, and 7; at 3 and 6 weeks; and at 3, 6, and 12 months following infarction). Left ventricular volumes were determined using Simpson's biplane formula and normalized for body surface area. Wall motion score index and sphericity index were calculated for each study. Coronary angiography was performed before discharge. RESULTS: Preinfarction angina was detected in 39 of 119 patients. Initial echocardiographic and clinical data as well as the incidence of patent infarct-related artery and collaterals were similar for patients with and without preinfarction angina. In the subset of thrombolysed patients, patients with preinfarction angina showed decrease of LV end-diastolic and end-systolic volumes during the follow-up period (p = 0.033 and p = 0.001, respectively), and improvement of wall motion score index (p < 0.001) and ejection fraction occurred (p = 0.001), without changing of LV shape (p > 0.05); in addition, patients with preinfarction angina had smaller LV volumes and higher ejection fraction than did those without angina, from 3 weeks onward. These favorable effects were not detected in patients not treated with thrombolysis. CONCLUSIONS: These data indicate that preinfarction angina has an inhibiting effect on long-term LV remodeling in patients who underwent thrombolysis for first acute myocardial infarction. It appears that preinfarction angina has no impact on infarct size and early postinfarction LV function.

Detection of massive pulmonary embolism by transesophageal echocardiography.

Transesophageal echocardiography is a new echocardiographic technique with indications that are still expanding and being redefined. Recently, the usefulness of transesophageal echocardiography in pulmonary embolism has been demonstrated in several case reports. In this article, we present 3 cases with pulmonary embolism diagnosed by transesophageal echocardiography and discuss its diagnostic value in this clinical setting.