Keywords

AHA’s life’s simple 7 (and Life’s Essential 8), Whole food plant-based Diet (WFBPD), Left ventricular internal diameters (LVID), Left ventricular ejection fraction (LVEF)

Introduction

There have been concerning trends in the incidence and prevalence of heart failure (HF) hospitalizations and mortality over the past few decades. According to the NHANES 2017-2020, approximately 6.7 million Americans over 20 years of age have HF. This is expected to rise to 8.5 million by 2030. The prevalence of HF among US adults is approximately 1.9% to 2.6% for the overall population and is higher among older patients, which is expected to increase to 8.5% among 65 to 70-year-olds [1]. With 6.7 million HF patients in US in 2020, an all-cause annual mortality rate has been estimated to be 9%. In a study from GWTG (Get With The Guidelines) registry of 39,982 patients hospitalized with HF with linked Medicare data and following through 2014 in risk-adjusted survival analysis, patients with HFrEF, HF with mildly reduced EF (HFmrEF, left ventricular EF 41%-49%) and HFpEF had similar 5-year mortality: 75.3%, 75.7%, and 75.7%, respectively [hazard ratio 0.99, 95% CI 0.97-1.046] [2,3]. As the risk factors for HF, such as obesity, diabetes, hypertension, hypercholesterolemia, and exposure to cardiotoxicity increase; the burden of HF will likely to increase. Despite expansion of guideline directed medical therapy (GDMT), the mortality rate and rehospitalization rate for HF remain high. An estimated 90% of the $4.3 trillion annual cost of health care in the United States is spent on medical care for chronic disease management. For many of these diseases, diet is a major risk factor, so modest improvements in diet could have a significant impact on cost saving [4].

Incorporating American Heart Association’s “Life’s Simple 7” (and recently Life’s Essential 8) lifestyle choices [5,6], and healthy dietary interventions [7,8], in addition to pharmacologic management in HF, has the potential for improving these grim outcomes.

Patient Selection and Method

In this prospective observational study from 1998 through 2023 in a cohort of 132 patients with low left ventricular ejection fraction (LVEF < 50%) have been treated and followed longitudinally by a single provider (GP) in the Cardiovascular Wellness Clinic. They were divided in to two groups: Group A, who have improved their LVEF by 10% or greater compared to the LVEF at baseline (responders, n = 101) and the Group B patients who have not achieved improvement and/or have decline in LVEF compared to the baseline LVEF (non-responders, n = 31), despite similar treatments. The Group B patients have end stage cardiomyopathy, advanced renal disease, medical noncompliance, and been treated for various cancers; and this may explain their non-response to treatment. The outcome of patients in Group A (responders) is the major focus of this study.

All the patients in this study have received GDMT - Beta-blockers, ACE inhibitors, ARB agents, ARNI agents, Aldosterone blockers, SGLT2 inhibitors, hydralazine/isordil, and diuretics as indicated. In addition to these medical treatments, they have been counseled on making appropriate lifestyle changes based on the AHA’s Life’s Simple 7 parameters (and since 2022, Life’s Essential 8 principles are adopted [9]). These include: 1) Heart healthy diet - mostly whole food plant-based diet (vegetables, fruits, beans, whole grains, seeds and nuts), and minimally processed foods. They were advised to avoid - meat, eggs, cheese, oil, added fat, added sugar, and high-fat milk. They are particularly recommended to avoid ultra processed foods and drinks (UPFD) [10], 2) Weight control with the goal of achieving BMI less than 25 kg/m ² , 3) Engage in regular exercise of moderate-vigorous intensity/vigorous intensity of 150/75 minutes per week. In addition, they were encouraged to add resistance training at least 2 days a week, 4) They were counseled to avoid risky substances - tobacco, alcohol, and marijuana products, 5) They were counseled to maintain ideal blood pressure control of 120/80 mm of Hg, 6) The goals were to achieve good control of lipids - total cholesterol of less than 150 mg/dl, triglyceride level less than 150 mg/dl, HDL cholesterol level higher than 40 mg/dl in men and 50 mg/dl in women, 7) Control of fasting blood glucose level of less than 100 mg/dl, and HbA1c less than 6.0%. Most recently added lifestyle changes to include 8) Restorative sleep of 7-8 hours, and 9) Dealing with stress/anxiety with mediation and relaxation techniques (my addition). These goals were discussed with each office visit to gauge their progress in adopting optimal lifestyle changes, and additional counseling were provided when needed. They were encouraged to monitor their weight, blood pressure, physical activities, and to comply with the prescribed diet. They were asked to bring along the entries of their weight and blood pressure records to the next clinic visit for discussion. Their progress was closely monitored with clinic visits at 3 months, 6 months, and at 12 months based upon their clinical need and progress. Blood chemistries which included - basal metabolic profile, liver function studies, lipid profile, and when indicated HbA1c, and were done prior to the clinic visits.

In addition, echocardiographic studies were done periodically based on the clinical progress, symptoms, and to gauge response to treatment with measurements of left ventricular end-diastolic and end-systolic dimensions, and measurement of EF calculated based on the Simpson’s bi-plane method.

Emphasis had been made on educating the patients in the cardiovascular disease process with reference to heart failure using animation. They were educated on diet (WFPB) by means of pamphlets, meal plans, label reading - to avoid saturated fat, high cholesterol, excess salt, and added sugar. Cooking methods of broiling, steaming, and roasting to preserve nutritional value were encouraged, and to use minimal or no oil in food preparation (instead using water or vegetable broth). The composition of meal planning incorporated to the breakdown of calories to nearly 75% complex carbohydrates, 15% plant protein, and 10% fat. Additionally, they were educated on high fiber containing foods to maximize intake of 40 grams of fiber daily for men and 30 grams for women [11-14].

Statistical Analysis

The statistical data analysis has been done by using Microsoft Excel statistical analysis package. Data are reported as mean and 1 SD. Intra-group analysis are done using the Student’s t-test, and p-value < 0.05 is considered significant.

Result

Group A cohort

This analysis includes 101 patients managed in the cardiovascular wellness clinic from 1998 through 2023, and were identified as showing positive improvements in left ventricular function following lifestyle treatment. Mean age of patients in the study was 67.6 years, ranging from age 39 to 95. The cohort consisted of 62 men and 39 women. The average time between baseline and final measurements was 12.5 years. Individuals in this cohort had diagnoses of non-ischemic cardiomyopathy (n = 55), ischemic cardiomyopathy (n = 33), and mixed cardiomyopathy (n = 13).

When comparing the mean baseline and final measurements in group A, significant decreases were found in heart rate: -7.47 bpm (p = < 0.0000), diastolic blood pressure: -5.58 mmHg (p = 0.0001), weight: -1.86 kg (p = 0.0283), BMI: -0.67 (p = 0.0130), total cholesterol: -19.14 mg/dL (p = 0.0002), LDL: -18.03 mg/dL (p = 0.0001), LVIDd (left ventricular diameter in diastole): -0.40 cm (p = < 0.0000), and LVIDs (left ventricular diameter in systole): -0.77 cm (p = < 0.0000). A significant increase was found in LVEF: 21.41% (p = < 0.0000) (Table 1).

When comparing the mean baseline and final measurements of those previously diagnosed with non-ischemic cardiomyopathy (NICM), significant decreases were found in heart rate: -7.81 bpm (p = 0.0023), diastolic blood pressure: -5.66 mmHg (p = 0.0013), total cholesterol: -19.91 mg/dL (p = 0.0109), LDL: -19.51 mg/dL (p = 0.0055), LVIDd: -0.44 cm (p = < 0.0000), and LVIDs: -0.86 cm (p = < 0.0000). A significant increase was found in LVEF: 22.65% (p = < 0.0000) (Table 2).

When comparing the mean baseline and final measurements of those previously diagnosed with ischemic cardiomyopathy (ICM), significant decreases were found in heart rate: -5.51 bpm (p = 0.0098), diastolic blood pressure: -29.99 mmHg (p = 0.0172), weight: -3.13 kg (p = 0.0337), BMI: -1.02 (p = 0.0443), total cholesterol: -18.09 mg/dL (p = 0.0130), LDL: -15.84 mg/dL (p = 0.0163), LVIDd: -0.35 cm (p = < 0.0012), and LVIDs: -0.64 cm (p = < 0.0000). A significant increase was found in LVEF: 19.73% [p = < 0.0000] (Table 2).

When comparing the mean baseline and final measurements of those previously diagnosed with mixed cardiomyopathy, significant decreases were found in heart rate: -11.00 bpm (p = 0.0270), weight: -4.58 kg (p = 0.0364), BMI: -1.43 (p = 0.0291), and LVIDs: -0.67 cm (p = < 0.0000). A significant increase was found in LVEF: 20.46% [p = < 0.0000] (Table 2).

The increase in LVEF from the baseline to the final evaluation after treatment (Figure 1) is inversely correlated with decrease in BMI, decrease in diastolic blood pressure, reduced total cholesterol, and reduced LDL cholesterol (Figure 2).

A case of NICM is illustrated with the left ventricular echocardiographic findings before treatment (baseline) and after treatment (final), along with the coronary angiography at baseline in Figure 3.1. Similarly, a case of ICM is illustrated in Figure 3.2.

Group B cohort

This cohort consists of 31 patients with the mean age of 69.3 years, ranging from 47 years to 94 years, and 19 were men and were 12 women. Their characteristics are included in Table 3.

In Table 4, the incidence of different categories of cardiomyopathy, utilization of pharmacological agents and CRT (Cardiac Resynchronization Therapy) between the two groups are summarized (Table 4). These treatments were similar between the two groups.

Discussion

The pathophysiology of heart failure (HF) with reduced ejection fraction (HRrEF) can be categorized in to two main groups - the group with genetic predisposition and the group with lifestyle related abnormalities [15]. Even some in the genetic predisposition group can benefit by lifestyle changes altering the epigenetic make up in improving heart function. The current management in HF is based on pharmacotherapy targeted at the neurohormonal abnormalities (the Hypothalamus-Pituitary-Adrenal axis - HPA, and the Renin-Angiotensin-Aldosterone System-RAAS) associated with myocardial dysfunction, but also myocardial dysfunction is due to a state of chronic inflammation with multitude of factors besides the neurohormonal alterations [9,16]. The inflammatory substrates have no effective medical treatment yet. But they can be improved with optimal lifestyle practices which include diet, exercise, weight control, abstinence from toxic chemicals, practice of appropriate sleep hygiene, and stress management [17]. Secondly, the current standard-of-care pharmacological approaches to HF provide symptomatic and clinical benefits by reducing workload on the heart instead of increasing its reserve where lifestyle changes will contribute by making cellular changes at molecular level [18].

Diet and nutrition

In the Cardiovascular Health status evaluation by the National Health and Nutrition Examination Survey (NHANES) between 2013-2018 in US adults, by the scored analysis according to the Life’s Essential 8 Metrics, it was found that only 36% percent of adult population has adopted a heart healthy dietary pattern [6]. Similarly, Baraldi, et al. have analyzed the data from the NHANES 2007-2012 period found that almost 60% of calories consumed came from ultra-processed foods and sugar containing drinks (UPFD) in the USA [19]. These studies have demonstrated that the dietary contribution of UPFD is inversely associated with low dietary content of protein, fiber, and most macronutrients, and are directly associated with high simple carbohydrate, saturated fat, total sugar, added sugar, and sodium content. An increase in dietary contribution of UPFDs have also been associated with decrease in vitamins A, C, D, and E, zinc, potassium, phosphorus, magnesium and calcium [19]. Secondly, the adverse health effects of the additives present in the UPFD are vastly unknown. But the recent research publication on Xylitol (low-calorie sweetener) is found to be associated with major cardiovascular risks and is a cause of concern for the other additives which have not been meticulously studied [20].

Improving current dietary habits to a WFPBD will have profound and positive health benefits in consuming appropriate number of calories from the macro and micronutrients. In addition, it provides high-fiber, minerals, vitamins, antioxidants, and bioflavonoids which are essential to maintain good health - energy balance, metabolism, support the gut microbiome, and improve immunity [21,22].

Heart failure is a myocardial nutrition deficiency disease, and for its metabolic and functional recovery, the biochemical needs are met with WFPBD, which is nutritionally rich, and is low in saturated fat, low in salt, and low in (added) sugar, and has no cholesterol.

Exercise

Physical activity in patients with HFrEF has pleotropic benefits. At minimum moderate-intensity/vigorous-intensity exercise duration of 150/75 minutes per week are recommended [23]. In addition, resistance training at least two days a week has added benefits in maintaining muscle mass and muscle strength. According to the NAHANES 2013-2018 data, only 52% of adults meet the minimum requirement of physical activity to maintain heart health [6]. Exercise training leads to improvements in central hemodynamic status and peripheral vascular, endothelial, and skeletal muscle function, attenuation of sympathetic, increase in vagal tone, and decrease in the neurohormonal activation (reduction in renin, angiotensin, and aldosterone). Other benefits are - reduction in circulating levels of N-terminal pro-B-type natriuretic peptide, reduced inflammatory cytokines, decrease in insulin resistance, decrease in lipids and blood pressure. Recent studies in rats have elucidated the dynamics of the multi-omic response to endurance training demonstrating, at cellular level, in enriching carbohydrate metabolism, oxidative phosphorylation and increased mitochondrial biogenesis. Besides these intracellular improvements, it has also regulated extracellular structural remodeling in promoting physiologically beneficial adaptations [reverse remodeling] [24]. These are accompanied with improvements in left-ventricular end-diastolic and end-systolic dimensions and LVEF. In addition, these favorable changes are associated with improvements in quality of life, functional capacity, exercise performance, and in modest reduction of heart failure related hospitalization and cardiovascular mortality [25-27].

Restoring metabolic balance and impact of autophagy

Obesity [28,29], diabetes, hypertension, and hyperlipidemia are the result of a poor-quality diet and suboptimal practice of healthy lifestyle and are responsible for most of the chronic diseases in our society today including heart disease [5]. At cellular level, these lead to lipotoxicity, oxidative stress, and myocardial dysfunction [30-34]. These can be remedied by the adoption of healthy lifestyle practices, including a predominantly a plant-based diet [35-38].

Autophagy, the self-eating activity involved in the maintenance of cellular homeostasis, is currently a therapeutic target in several diseases, including heart failure. Enhancing autophagy with regular exercise and intermittent fasting (and/or time restricted eating) are promising strategies in improving cellular function thereby improving left ventricular function in heart failure [39]. Heart muscle requires perennial energy production and utilization. In this process, equally significant wear and tear of intracellular organelles, and excess toxic metabolic byproducts are generated. As a result, heart is a unique organ having dual mechanisms of autophagic process both intracellular (lysosome) and extracellular (material spilling over from the crowded intramyocellular compartment to extracellular space are cleared by the macrophages), to deal with these inflammatory byproducts, cellular debris, and importantly in recycling some of the essential components (proteins), thereby saving energy [40].

Tobacco, cannabis, and alcohol

Smoking cigarettes, cannabis, and drinking excess alcohol are all linked to heart failure. Cigarette smoking leads to vascular endothelial dysfunction and coronary artery disease a major cause for heart failure, myocardial infarction and cardiac arrhythmia. Cannabis has multiple effects in the cardiovascular system. Tetrahydrocannabinol (THC) stimulates the sympathetic system; increase heart rate, myocardial oxygen demand, supine blood pressure, and platelet activation; and associated with endothelial dysfunction and oxidative stress. Smoking cannabis regardless of THC content increase concentration of carboxyhemoglobin and tar. These lead to endothelial dysfunction, increased oxidation of lipoproteins leading to clinical presentations of cardiomyopathy, angina, myocardial infarction, arrhythmia, heart failure and sudden cardiac death [41]. Excess alcohol consumption combined with unhealthy diet leads to cardiomyopathy and heart failure [42,43]. The pathology of alcoholic cardiomyopathy involves a combination of direct toxic effects of alcohol on the myocardium, oxidative stress, mitochondrial dysfunction, and a genetic susceptibility. Ethanol and its metabolites can disrupt cellular processes, impair protein synthesis, and cause oxidative stress leading to cellular injury and dysfunction within the heart muscle [44]. Moreover, there has been causal association between alcohol consumption and risk of hypertension, especially an alcohol intake of 12 g/d, and are consistent with recommendations to avoid or limit alcohol intake. Besides the direct myocardial toxicity of alcohol leading to cardiomyopathy, hypertension is also a major risk factor for developing cardiomyopathy [45]. On the other hand, abstaining from alcohol use and adhering to a healthy lifestyle as outlined in the “Life’s Simple 7” will prevent and even reverse these serious health conditions.

Environmental stress- anxiety/depression

Environmental stress can lead to anxiety and depression. Chronic stress has been known to cause cardiovascular disease and other metabolic disorders mediated through activation of chronic inflammatory response by liberation of many cytokines - interleukin-1, IL-2, IL-4, tumor necrosis factor (TNF) alpha, and interferon (INF) alpha. These elements impair the function of the glucocorticoid receptor (GR) which is otherwise known as “glucocorticoid resistance”. This in turn leads to excessive inflammation as well as hyperactivity of the corticotrophin releasing hormone and sympathetic system pathways. These ultimately contribute to variety of diseases and behavioral alterations responsible in perpetuating the process [46]. In a human genome-wide study, impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways has provided a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective isolation [chronic stress] [47]. It has been found that long-term meditation practices have prevented and reversed the stress related harmful health effects by epigenetic alterations and influencing the gene expression positively [48,49].

Circadian rhythm and sleep duration

The circadian rhythm is an evolutionary regulatory mechanism that influences the expression of human biology and physiology to maintain homeostasis for optimal bodily function. This collates three major activities - time restricted eating, ideally a window of 8 to 10 hours over 24 hours (that is fasting 16 and 14 hours respectively), energy generation for physiologic and physical activities, and restorative sleep for 7 to 8 hours daily (allows cellular metabolic recovery, repair, autophagy, and rejuvenation). These taken together and practice with regularity maintains the integrity of cellular and overall organ function, which is essential for optimal health [50-53].

Conclusion

Incorporating lifestyle practices to standard medical management has the complementary advantage in recovering left ventricular structure and function. These changes are accompanied with reduced weight, improved metabolism, reduction in inflammation, improvement in cardiovascular hemodynamics, and ultimately achieving favorable outcomes by reversing left ventricular remodeling, improving myocardial dynamics, and thereby improving LVEF.

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