Krzysztof S. Golba

Navigating the Crossroads of Coronary Artery Disease and Heart Failure

Chronic heart failure (HF) affects 5 million patients in the United States and is responsible for &1 million hospitalizations and 300 000 deaths annually.1 The total annual costs associated with this disorder have been estimated to exceed

Ten-year probability of osteoporotic fracture in 2012 Polish women assessed by FRAX and nomogram by Nguyen et al.-Conformity between methods and their clinical utility.

40 billion.1,2 Chronic HF is the only category of cardiovascular diseases for which the prevalence, incidence, hospitalization rate, total burden of mortality, and costs have increased in the past 25 years.1,2 Fueling this epidemic is the increasing number of elderly patients developing impaired left ventricular (LV) function as a manifestation of chronic coronary artery disease (CAD).1,2 With the aging of the population and decline in mortality of other forms of cardiovascular diseases, it is likely that the incidence of HF and its impact on public health will continue to increase.1–3 In the past 3 decades, considerable attention has focused on LV dysfunction, loading conditions, neuroendocrine activation, and ventricular remodeling as the principal pathophysiological mechanisms underlying HF progression.4 There has been a fundamental shift, however, in the origin of HF that often is underemphasized.3–5 The Framingham Heart Study suggests that the most common cause of HF is no longer hypertension or valvular heart disease, as it was in previous decades, but rather CAD.4 This shift may be related to improved survival of patients after acute myocardial infarction (MI). Over the past 40 years in the United States, the odds of previous MI as a cause for HF increased by 26% per decade in men and 48% per decade in women. In contrast, there has been a 13% decrease per decade for hypertension as a cause of HF in men and a 25% decrease in women, as well as a decrease in valvular disease by 24% per decade in men and 17% in women. In the 24 …

Ten-Year Outcomes After Coronary Artery Bypass Grafting According to Age in Patients With Heart Failure and Left Ventricular Systolic Dysfunction: An Analysis of the Extended Follow-Up of the STICH Trial (Surgical Treatment for Ischemic Heart Failure).

PURPOSE The aim of the cross-sectional study was to establish the degree of conformity between 10-year probability of osteoporotic fracture, assessed by FRAX, and using the nomograms, as proposed by Nguyen at al. METHODS Postmenopausal Polish women (2012) were examined in their mean age of 68.5+/-7.9 years (age range 55-90 years). Fracture probability by FRAX was based on age, BMI, prior fracture, hip fracture in parents, steroid use, rheumatoid arthritis, alcohol use, secondary osteoporosis and T-score for femoral neck BMD. Fracture probability by Nguyens nomograms was based on age, the number of prior fractures, the number of falls and T-score for femoral neck BMD. RESULTS The mean conformity rate was 79.1% for any fracture risk (for threshold 20%) and 79.5% for hip fracture (threshold 3%). Any and hip fracture risks were significantly higher for both methods in women with fracture history in comparison to those without fracture and increased with ageing. The influence of prior fracture and ageing was more evident in Nguyens nomograms. ROC analyses of any fracture risk in FRAX and Nguyens methods demonstrated the area under curve (AUC) at 0.833 and 0.879, respectively. Similar analyses for hip fracture demonstrated AUCs for FRAX and Nguyens technique at 0.726 and 0.850, respectively. The AUCs for Nguyens nomograms were significantly larger than the AUCs for FRAX (p<0.0001). CONCLUSION The mean conformity for any fracture risk is 79.1% and 79.5% for hip fracture. Nguyens nomograms seem to be more efficient in fracture risk assessment, especially for hip fractures, due to a higher accuracy of the method. The information on the number of falls during the last year and multiple fractures ought to be incorporated into the method of fracture risk prediction. MINI-ABSTRACT The degree of conformity was assessed in a group of 2012 women between 10-year FRAX prognosis of fracture and Nguyen et al.s nomograms. The mean conformity for any fracture risk is 79.1% and 79.5% for hip fracture. Nguyens nomograms seem to be more efficient in fracture risk assessment due to higher accuracy.

Diazoxide protects myocardial mitochondria, metabolism, and function during cardiac surgery: A double-blind randomized feasibility study of diazoxide-supplemented cardioplegia

Background: Advancing age is associated with a greater prevalence of coronary artery disease in heart failure with reduced ejection fraction and with a higher risk of complications after coronary artery bypass grafting (CABG). Whether the efficacy of CABG compared with medical therapy (MED) in patients with heart failure caused by ischemic cardiomyopathy is the same in patients of different ages is unknown. Methods: A total of 1212 patients (median follow-up, 9.8 years) with ejection fraction ⩽35% and coronary disease amenable to CABG were randomized to CABG or MED in the STICH trial (Surgical Treatment for Ischemic Heart Failure). Results: Mean age at trial entry was 60 years; 12% were women; 36% were nonwhite; and the baseline ejection fraction was 28%. For the present analyses, patients were categorized by age quartiles: quartile 1, ⩽54 years; quartile, 2 >54 and ⩽60 years; quartile 3, >60 and ⩽67 years; and quartile 4, >67 years. Older versus younger patients had more comorbidities. All-cause mortality was higher in older compared with younger patients assigned to MED (79% versus 60% for quartiles 4 and 1, respectively; log-rank P=0.005) and CABG (68% versus 48% for quartiles 4 and 1, respectively; log-rank P<0.001). In contrast, cardiovascular mortality was not statistically significantly different across the spectrum of age in the MED group (53% versus 49% for quartiles 4 and 1, respectively; log-rank P=0.388) or CABG group (39% versus 35% for quartiles 4 and 1, respectively; log-rank P=0.103). Cardiovascular deaths accounted for a greater proportion of deaths in the youngest versus oldest quartile (79% versus 62%). The effect of CABG versus MED on all-cause mortality tended to diminish with increasing age (Pinteraction=0.062), whereas the benefit of CABG on cardiovascular mortality was consistent over all ages (Pinteraction=0.307). There was a greater reduction in all-cause mortality or cardiovascular hospitalization with CABG versus MED in younger compared with older patients (Pinteraction=0.004). In the CABG group, cardiopulmonary bypass time or days in intensive care did not differ for older versus younger patients. Conclusions: CABG added to MED has a more substantial benefit on all-cause mortality and the combination of all-cause mortality and cardiovascular hospitalization in younger compared with older patients. CABG added to MED has a consistent beneficial effect on cardiovascular mortality regardless of age. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Mechanisms of Functional Mitral Regurgitation in Ischemic Cardiomyopathy Determined by Transesophageal Echocardiography (from the Surgical Treatment for Ischemic Heart Failure Trial)

OBJECTIVES The study was designed to assess whether diazoxide-mediated cardioprotection might be used in human subjects during cardiac surgery. METHODS Forty patients undergoing coronary artery bypass grafting were randomized to receive intermittent warm blood antegrade cardioplegia supplemented with either diazoxide (100 micromol/L) or placebo (n = 20 in each group). Mitochondria were assessed before and after ischemia and reperfusion in myocardial biopsy specimens. Myocardial oxygen and glucose and lactic acid extraction ratios were measured before ischemia and in the first 20 minutes of reperfusion. Hemodynamic data were collected, and troponin I, creatine kinase-MB, and N-terminal prohormone brain natriuretic peptide levels were measured. All outcomes were analyzed by using mixed-effects modeling for repeated measures. RESULTS No deaths, strokes, or infarcts were observed. Patients received, on average, 36.2 +/- 1.2 mg of diazoxide and 37.3 +/- 1.9 mg of placebo (P = .6). Diazoxide added to cardioplegia prevented mitochondrial swelling (8899 +/- 474 vs 9273 +/- 688 pixels before and after the procedure, respectively; P = .6) compared with that seen in the placebo group (8474 +/- 163 vs 11,357 +/- 759 pixels, P = .004). No oxygen debt was observed in the diazoxide group. Glucose consumption and lactic acid production returned to preischemic values faster in the diazoxide group. The following hemodynamic parameters differed between the diazoxide and placebo groups, respectively, in the postoperative period: cardiac index, 3.0 +/- 0.09 versus 2.6 +/- 0.09 L . min(-1) . m(-2) (P = .002); left cardiac work index, 2.81 +/- 0.07 versus 2.31 +/- 0.07 kg/m(2) (P < .001); oxygen delivery index, 420 +/- 14 versus 377 +/- 13 mL . min(-1) . m(-2) (P = .03); and oxygen extraction ratio, 29.3% +/- 1.1% versus 32.6% +/- 1.1% (P = .02). Postoperative myocardial enzyme levels did not differ, but N-terminal prohormone brain natriuretic peptide levels were lower in the diazoxide group (120 +/- 27 vs 192 +/- 29 pg/mL, P = .04). CONCLUSIONS Supplementing blood cardioplegia with diazoxide is safe and improves myocardial protection during cardiac surgery, possibly through its influence on the mitochondria.

Diazoxide provides protection to human myocardium in vitro that is concentration dependent

The mechanisms underlying functional mitral regurgitation (MR) and the relation between mechanism and severity of MR have not been evaluated in a large, multicenter, randomized controlled trial. Transesophageal echocardiography (TEE) was performed in 215 patients at 17 centers in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Both 2-dimensional (n = 215) and 3-dimensional (n = 81) TEEs were used to assess multiple quantitative measurements of the mechanism and severity of MR. By 2-dimensional TEE, leaflet tenting area, anterior and posterior leaflet angles, mitral annulus diameter, left ventricular (LV) end-systolic volume index, LV ejection fraction (LVEF), and sphericity index (p <0.05 for all) were significantly different across MR grades. By 3-dimensional TEE, mitral annulus area, leaflet tenting area, LV end-systolic volume index, LVEF, and sphericity index (p <0.05 for all) were significantly different across MR grades. A multivariate analysis showed a trend for annulus area (p = 0.069) and LV end-systolic volume index (p = 0.071) to predict effective regurgitant orifice area and for annulus area (p = 0.018) and LV end-systolic volume index (p = 0.073) to predict vena contracta area. In the STICH trial, multiple quantitative parameters of the mechanism of functional MR are related to MR severity. The mechanism of functional MR in ischemic cardiomyopathy is heterogeneous, but no single variable stands out as a strong predictor of quantitative severity of MR.

Statistical agreement of left ventricle measurements using cardiac magnetic resonance and 2D echocardiography in ischemic heart failure

BACKGROUND Diazoxide has been shown to confer significant myocardial protection in many experiments. This study was designed to assess its influence on the structural injury and functional recovery of human myocardium subjected to hypoxia/reoxygenation in vitro. METHODS The isolated electrically driven human right atrial trabeculae, obtained during cardiac surgery, were studied. The tissue bath was oxygenated with 95% oxygen and 5% carbon dioxide, hypoxia being obtained by replacing oxygen with argon. The influence of diazoxide on atrial contractility was studied first. Next, the two trabeculae from one atrial appendage were studied simultaneously, adding diazoxide to the tissue bath 10 minutes before hypoxia in one, with another serving as a control. We tested 10(-4.5) mol/L and 10(-4) mol/L diazoxide in three sets of experiments testing 30, 60, and 90 minutes of hypoxia. We continued reoxygenation for 120 minutes (in 60-minute and 90-minute hypoxia experiments) and subsequently tested reaction to 10(-4) mol/L norepinephrine. Apart from continuous recording of the contraction force, we measured the troponin I release into the tissue bath after ischemia and reoxygenation. RESULTS Diazoxide exerted a negative inotropic effect in human atrial muscle (pD(2)=3.96 +/- 0.18). Both concentrations of diazoxide studied resulted in better functional recovery of atrial trabeculae subjected to 30 minutes of hypoxia. With longer hypoxia, only the higher diazoxide concentration provided significant protection as assessed by contractility. After 120 minutes of reoxygenation, only diazoxide-treated muscle was viable enough to respond to norepinephrine. Only 10(-4) mol/L diazoxide resulted in lower troponin I release during hypoxia and reoxygenation. CONCLUSIONS This study shows that diazoxide provides significant concentration-dependent protection against hypoxia/reoxygenation injury to human myocardium in vitro.

Frailty Syndrome in Heart Failure Patients who are Receiving Cardiac Resynchronization.

Summary Background The aim of this study was to compare cardiac magnetic resonance imaging (CMR) with 2-dimensional echocardiography (2D echo) in the assessment of left ventricle (LV) function parameters and mass in patients with ischemic heart disease and severely depressed LV function. Although 2D echo is commonly used to assess LV indices, CMR is the state-of-the-art technique. Agreement between these 2 methods in these patients has not been well established. Material/Methods LV indexed end systolic and diastolic volumes (EDVi and ESVi), indexed mass (LVMi) and ejection fraction (EF) were assessed in 67 patients (12 women), using 2D echo and CMR. Results According to statistical analysis (Bland-Altman), 2D echo underestimated LV EDV and ESV and overestimated EF and LVMi compared to CMR. The highest correlation between 2D echo and CMR was found for EDVi (R2=0.73, p<0.0001) and ESVi (R2=0.69, p<0.0001) and the lowest for EF (R2=0.21, p=0.001) and LVMi (R2=0.20, p=0.002). The maximal differences between 2D echo and CMR were found for highest mesurements of LV volumes and mass, and for lowest EF values. Conclusions There is moderate to strong correlation between CMR and 2D echo in the assessment of LV function parameters and mass in patients with ischemic heart failure. Between-method agreement depends on the degree of LV dysfunction. The results of assessment of the severely damaged LV obtained by the use of 2D echo should be interpreted with caution.

Gastric tonometry as a method of visceral oxygenation monitoring in patients undergoing coronary revascularisation.

We hypothesized that patients with de novo cardiac resynchronization therapy (CRT) implantation had a more intense frailty syndrome when compared to the patients who qualified for a system upgrade.

Left internal mammary artery improves 5-year survival in patients under 40 subjected to surgical revascularization.

OBJECTIVE The aim of the study was to assess gastric mucosal pH during certain parts of a major cardiac procedure (hypo- and normothermic), and then throughout the first postoperative day. METHODS Gastric mucosal pH was measured using a tonometer, in 15 patients subjected to elective CABG procedures. The patients were also assessed haemodynamically and serum lactate concentrations were measured. RESULTS It was found that cardiopulmonary bypass did not suppress visceral perfusion. The most critical was the period between 4th and 12th postbypass hour when a tendency towards decreased cardiac output and oxygen delivery was noted. At the same time oxygen consumption was increasing which resulted in triggering of anaerobic metabolic pathways, that was mirrored by significant rise in serum lactate levels. During this period of time the lowest, although not critical levels of gastric mucosal pH were recorded, suggesting a relative decrease in splanchnic perfusion. CONCLUSION Extracorporeal circulation does not significantly compromise splanchnic perfusion. Tonometry is a valuable, non-invasive method of visceral oxygenation monitoring. The first postoperative day is an especially critical time for a cardiac patient--a frequent control of haemodynamic and acid-base balance parameters is absolutely mandatory.