-
1.
Obesity-related heart failure with preserved ejection fraction: new treatment strategies.
Chrysant, SG, Chrysant, GS
Hospital practice (1995). 2019;(2):67-72
Abstract
OBJECTIVES Obesity has risen in the US and worldwide, and has become a major risk factor for type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease, and mostly HF with preserved ejection fraction (HFpEF). Also, the prevalence of HF is quite high in the US accounting for 6.6 million adults at present and is projected to reach 8.5 million by the year 2030 and is equally divided between HFpEF and heart failure reduced ejection fraction (HFrEF). Patients with HFpEF are resistant to treatment with drugs usually used for the treatment of HFrEF, but the reasons for this resistance are not clearly known. METHODS In order to get a better perspective on the current status of the underlying pathophysiology and treatment of patients with HFpEF, a Medline search of the English language literature was conducted between 2015 and 2018 using the terms obesity, HFpEF, diabetes, treatment, SGLT2 inhibitors, and neprilysin inhibitors and 24 pertinent papers were selected. RESULTS The review of these papers revealed that patients with HFpEF have expanded plasma volume, restricted left ventricular distension with increased end-diastolic volume and depressed natriuretic peptide levels. In this respect, drugs that cause increased diuresis and natriuresis should a reasonable choice to treat these patients. The recently FDA approved sodium-glucose cotransporter-2 (SGLT2) inhibitors for the treatment of T2DM, are a good choice, for the treatment of HFpEF, since they cause osmotic diuresis from glucose excretion and increase salt and water excretion and decrease plasma volume. In addition, they produce loss of calories leading to weight and blood pressure reduction and have shown to prevent the new onset HFpEF and decrease hospitalizations and death from this disease. CONCLUSION The results of this analysis has shown that HFpEF has different pathophysiology from HFrEF and is difficult to treat. Drugs that block renal tubular glucose reabsorption and cause osmotic diuresis and natriuresis could be a good choice to treat patients with HFpEF alone or in combination with diuretics and other drugs.
-
2.
The predictors of no reflow phenomenon after percutaneous coronary intervention in patients with ST elevation myocardial infarction: A meta-analysis.
Fajar, JK, Heriansyah, T, Rohman, MS
Indian heart journal. 2018;(Suppl 3):S406-S418
Abstract
OBJECTIVE To investigate the no reflow risk factors after percutaneous coronary intervention in ST elevation myocardial infarction patients. METHOD Sample size, mean±standard deviation (SD) or frequencies (percent) of normal and no reflow groups were extracted from each study. RESULTS Of 27 retrospective and prospective studies, we found that increasing risks of no reflow were associated with advanced age, male, family history of coronary artery disease, smoking, diabetes mellitus, hypertension, delayed reperfusion, killip class ≥2, elevated blood glucose, increased creatinine, elevated creatine kinase (CK), higher heart rate, decreased left ventricular ejection fraction (LVEF), collateral flow ≤1, longer lesion length, multivessel disease, reference luminal diameter, initial thrombolysis in myocardial infarction (TIMI) flow, and high thrombus burden. Moreover, initial TIMI flow ≤1 and high thrombus burden had the greater impact on no reflow (OR95%CI=3.83 [2.77-5.29], p<0.0001 and 3.69 [2.39-5.68], p<0.0001, respectively). CONCLUSION Our meta-analysis reveals that initial TIMI flow ≤1 and high thrombus burden are the most impacted no reflow risk factors.
-
3.
Effects of Caffeine on Myocardial Blood Flow: A Systematic Review.
van Dijk, R, Ties, D, Kuijpers, D, van der Harst, P, Oudkerk, M
Nutrients. 2018;(8)
Abstract
Caffeine is one of the most widely consumed stimulants worldwide. It is a well-recognized antagonist of adenosine and a potential cause of false-negative functional measurements during vasodilator myocardial perfusion. The aim of this systematic review is to summarize the evidence regarding the effects of caffeine intake on functional measurements of myocardial perfusion in patients with suspected coronary artery disease. Pubmed, Web of Science, and Embase were searched using a predefined electronic search strategy. Participants-healthy subjects or patients with known or suspected CAD. Comparisons-recent caffeine intake versus no caffeine intake. Outcomes-measurements of functional myocardial perfusion. Study design-observational. Fourteen studies were deemed eligible for this systematic review. There was a wide range of variability in study design with varying imaging modalities, vasodilator agents, serum concentrations of caffeine, and primary outcome measurements. The available data indicate a significant influence of recent caffeine intake on cardiac perfusion measurements during adenosine and dipyridamole induced hyperemia. These effects have the potential to affect the clinical decision making by re-classification to different risk-categories.
-
4.
New and revisited approaches to preserving the reperfused myocardium.
Kloner, RA, Brown, DA, Csete, M, Dai, W, Downey, JM, Gottlieb, RA, Hale, SL, Shi, J
Nature reviews. Cardiology. 2017;(11):679-693
-
-
Free full text
-
Abstract
Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse remodelling of the heart in the months that follow. Given that attempts to further reduce myocardial infarct size beyond early reperfusion in clinical trials have so far been disappointing, effective therapies are still needed to protect the reperfused myocardium. In this Review, we discuss several approaches to preserving the reperfused heart, such as therapies that target the mechanisms involved in mitochondrial bioenergetics, pyroptosis, and autophagy, as well as treatments that harness the cardioprotective properties of inhaled anaesthetic agents. We also discuss potential therapies focused on correcting the no-reflow phenomenon and its effect on healing and adverse left ventricular remodelling.
-
5.
Pharmacotherapy for coronary microvascular dysfunction.
Ong, P, Athanasiadis, A, Sechtem, U
European heart journal. Cardiovascular pharmacotherapy. 2015;(1):65-71
Abstract
Coronary microvascular dysfunction (CMD) has been increasingly recognized as an important cardiac condition that can cause signs and symptoms of myocardial ischaemia in various clinical settings. The dysfunction is located on the level of the coronary microcirculation with a vessel diameter of <500 µm and can be characterized by structural as well as functional vascular alterations. The underlying mechanisms are diverse, frequently overlapping and still incompletely understood. A common and often underdiagnosed clinical manifestation of CMD is in patients who have angina symptoms yet no obstructive epicardial coronary artery disease nor myocardial disease. There are still very few data regarding the effectiveness of pharmacological treatments for CMD. The current ESC guidelines on the management of stable coronary artery disease suggest using aspirin and statins as well as β-blockers and/or calcium-channel blockers for the treatment of CMD. This review gives an overview of the currently available pharmacological concepts for the treatment of coronary microvascular dysfunction in patients without epicardial coronary artery disease and without myocardial disease.
-
6.
Impact of obesity and bariatric surgery on metabolism and coronary circulatory function.
Valenta, I, Dilsizian, V, Quercioli, A, Jüngling, FD, Ambrosio, G, Wahl, R, Schindler, TH
Current cardiology reports. 2014;(1):433
Abstract
Increases in intra-abdominal visceral adipose tissue have been widely appreciated as a risk factor for metabolic disorders such as dyslipidemia, hypertension, insulin resistance, and type 2 diabetes, whereas this is not the case for peripheral or subcutaneous obesity. While the underlying mechanisms that contribute to these differences in adipose tissue activity remain uncertain, increases in visceral fat commonly induce metabolic dysregulation, in part because of increased venous effluent of fatty acids and/or adipokines/cytokines to the liver. Increased body weight, paralleled by an increase in plasma markers of the insulin-resistance syndrome and chronic inflammation, is independently associated with coronary circulatory dysfunction. Recent data suggest that plasma proteins originating from the adipose tissue, such as endocannabinoids (EC), leptin, and adiponectin (termed adipocytes) play a central role in the regulation and control of coronary circulatory function in obesity. Positron emission tomography (PET) in concert with tracer kinetic modeling is a well established technique for quantifying regional myocardial blood flow at rest and in response to various forms of vasomotor stress. Myocardial flow reserve assessed by PET provides a noninvasive surrogate of coronary circulatory function. PET also enables the monitoring and characterization of coronary circulatory function in response to gastric bypass-induced weight loss in initially morbidly obese individuals, to medication and/or behavioral interventions related to weight, diet, and physical activity. Whether the observed improvement in coronary circulatory dysfunction via weight loss may translate to diminution in cardiovascular events awaits clinical confirmation.
-
7.
Short-term effect of verapamil on coronary no-reflow associated with percutaneous coronary intervention in patients with acute coronary syndrome: a systematic review and meta-analysis of randomized controlled trials.
Su, Q, Li, L, Liu, Y
Clinical cardiology. 2013;(8):E11-6
Abstract
BACKGROUND To evaluate the clinical efficacy and safety of intracoronary verapamil injection in the prevention and treatment of coronary no-reflow after percutaneous coronary intervention (PCI). HYPOTHESIS Intracoronary verapamil injection may be beneficial in preventing no-reflow/slow-flow after PCI. METHODS We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials database. Randomized trials comparing the efficacy and safety of intracoronary verapamil infusion vs control in patients with acute coronary syndrome (ACS) were included. Meta-analysis was performed by RevMan 5.0 software (Cochrane Collaboration, Copenhagen, Denmark) . RESULTS Seven trials involving 539 patients were included in the analysis. Verapamil treatment was significantly more effective in decreasing the incidence of no-reflow (risk ratio [RR]: 0.33; 95% confidence interval [CI]: 0.23 to 0.50) as well as reducing the corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) (weighted mean difference: -11.62; 95% CI: -16.04 to -7.21) and improving the TIMI myocardial perfusion grade (TMPG) (RR: 0.43; 95% CI: 0.29 to 0.64). Verapamil also reduced the 30-day wall motion index (WMI) compared to the control. Moreover, the procedure reduced the incidence of major adverse cardiac events (MACEs) in ACS patients during hospitalization (RR: 0.37; 95% CI: 0.17 to 0.80) and 2 months after PCI (RR: 0.56; 95% CI: 0.33 to 0.95). However, administration of verapamil did not provide an additional improvement of left ventricular ejection fraction regardless of the time that had passed post-PCI. CONCLUSIONS Intracoronary verapamil injection is beneficial in preventing no-reflow/slow-flow, reducing CTFC, improving TMPG, and lowering WMI. It is also likely to reduce the 2-month MACEs in ACS patients post-PCI.
-
8.
Cyanotic congenital heart disease the coronary arterial circulation.
Perloff, JK
Current cardiology reviews. 2012;(1):1-5
-
-
Free full text
-
Abstract
BACKGROUND The coronary circulation in cyanotic congenital heart disease (CCHD) includes the extramural coronary arteries, basal coronary blood flow, flow reserve, the coronary microcirculation, and coronary atherogenesis. METHODS Coronary arteriograms were analyzed in 59 adults with CCHD. Dilated extramural coronaries were examined histologically in six patients. Basal coronary blood flow was determined with N-13 positron emission tomography in 14 patients and in 10 controls. Hyperemic flow was induced by intravenous dipyridamole pharmacologic stress. Immunostaining against SM alpha-actin permitted microcirculatory morphometric analysis. Non-fasting total cholesterols were retrieved in 279 patients divided into four groups: Group A---143 cyanotic unoperated, Group B---47 rendered acyanotic by reparative surgery, Group C---41 acyanotic unoperated, Group D---48 acyanotic before and after operation. RESULTS Extramural coronary arteries were mildly or moderately dilated to ectatic in 49/59 angiograms. Histologic examination disclosed loss of medial smooth muscle, increased medial collagen, and duplication of internal elastic lamina. Basal coronary flow was appreciably increased. Hyperemic flow was comparable to controls. Remodeling of the microcirculation was based upon coronary arteriolar length, volume and surface densities. Coronary atherosclerosis was absent in both the arteriograms and the necropsy specimens. CONCLUSIONS Extramural coronary arteries in CCHD dilate in response to endothelial vasodilator substances supplemented by mural attenuation caused by medial abnormalities. Basal coronary flow was appreciably increased, but hyperemic flow was normal. Remodeling of the microcirculation was responsible for preservation of flow reserve. The coronaries were atheroma-free because of the salutory effects of hypocholesterolemia, hypoxemia, upregulated nitric oxide, low platelet counts, and hyperbilirubinrmia.
-
9.
Mechanisms of metabolic coronary flow regulation.
Deussen, A, Ohanyan, V, Jannasch, A, Yin, L, Chilian, W
Journal of molecular and cellular cardiology. 2012;(4):794-801
Abstract
Coronary blood flow is tightly adjusted to the oxygen requirements of the myocardium. The underlying control mechanisms keep coronary venous pO(2) at a rather constant level around 20mm Hg under a variety of physiological conditions. Because coronary flow may increase more than 5-fold during exercise without any signs of under- or overperfusion, coronary flow must be controlled, at least in part, in a feed forward manner. Likely metabolic factors contributing to feed forward control are carbon dioxide and reactive oxygen species. Adaptation of coronary flow to exercise under physiological conditions involves in addition to metabolic control feed forward neuronal and endothelium-dependent control. Under pathological conditions, e.g. vessel stenosis or anemia, or specific environmental conditions, e.g. high altitude exposure, cardiac oxygenation may become critical, especially if oxygen demand is increased during physical exercise. Under such conditions the fall of coronary pO(2) may directly result in opening of oxygen sensitive potassium or closure of calcium channels. Furthermore the fall of pO(2) results in the production of vasoactive metabolites, e.g. adenosine, nitric oxide or prostaglandins, and in proton accumulation. All of these adaptations support a reduction of coronary vessel resistance. This article is part of a Special Issue entitled "Coronoray Blood Flow".
-
10.
Control of coronary blood flow during hypoxemia.
Tune, JD
Advances in experimental medicine and biology. 2007;:25-39
Abstract
Coronary vascular resistance is regulated by a variety of factors including arterial pressure, myocardial metabolism, autonomic nervous system as well as arterial O2 tension (hypoxia). Progressive hypoxemia results in graded coronary vasodilation that is significantly more pronounced when arterial O2 tension falls below 40 mmHg. Microvascular studies have demonstrated that O2 has direct effects on vascular smooth muscle likely mediated by O2 sensors located in vessels <15 microm diameter. Recent data indicates that hypoxia-induced inhibition of the pentose phosphate pathway and the subsequent decreases in NADPH and intracellular Ca2+ represent an important O2 sensing mechanism in vascular smooth muscle. However, in vivo experiments suggest direct microvascular effects of O2 contribute little to hypoxic coronary vasodilation. The vasodilation is mediated, in part, by local vasoactive metabolites produced in proportion to the degree of hypoxemia, reflex-mediated increases in myocardial metabolism and diminished myocardial tissue oxygenation. In particular, production of adenosine has been shown to increase exponentially with the degree of hypoxia and blockade or degradation of adenosine markedly impairs hypoxia-induced coronary vasodilation. Other investigations support the role of endothelial derived relaxing factors (nitric oxide, prostacyclin) in control of coronary blood flow during hypoxia. Additionally, reductions in PO2 hyperpolarize coronary vascular smooth muscle via K+(ATP) channels which represent important "end effectors" that significantly contribute to hypoxic coronary vasodilation. Taken together, these data indicate that the coronary vascular response to hypoxia depends on metabolic and endothelial vasodilatory factors that are produced in proportion to the degree of hypoxemia and that function through mechanisms depending on K+(ATP), channels.