Natural history of superior mesenteric artery in-stent restenosis.

OBJECTIVE: Superior mesenteric artery (SMA) stenting is the preferred approach for patients with symptomatic SMA-associated chronic mesenteric ischemia (CMI). The durability of this modality is impacted by in-stent restenosis (ISR). Duplex ultrasound (DUS) and computed tomographic angiography (CTA)-measured ISR may be weakly correlated and not uniformly associated with recurrence of presenting symptoms. This study aims to analyze the association between the degree of ISR for patients with CMI and to develop a predictive model for symptom recurrence. METHODS: Single center, retrospective study included all patients with CMI with SMA stents from the period of 2003 to 2020. Follow-up period analysis included patients' symptoms recurrence, DUS, CTA, and angiography. A receiver operating characteristic (ROC) analysis was used to evaluate whether peak systolic velocity (PSV) was predictive of symptom recurrence. A subgroup analysis of patients (asymptomatic and symptomatic) with SMA ISR was identified; restenosis defined by DUS with peak systolic velocity (PSV) ≥350. RESULTS: The study included 186 patients with the ROC analysis obtained from 503 postoperative visits. PSV was not a predictor of symptoms return with area under the curve (AUC) = 0.49 (95% confidence interval [CI], 0.40-0.57). Agreement analysis between imaging modalities showed higher agreement between CTA and angiogram (AUC, 0.769; 95% CI, 0.688-0.849) vs CTA and DUS (AUC, 0.650; 95% CI, 0.589-0.711). The subgroup analysis of patients with ISR included 99 patients (asymptomatic n = 67; symptomatic n = 32). There was no statistical difference between median time (months) to ISR between both groups: 4.5 (asymptomatic group) and 7.6 (symptomatic group). The use of preoperative antiplatelet (86% vs 65%; P = .015) and P2Y12 receptor blockers (36% vs 13%; P = .016) was more prevalent in the asymptomatic group. There was no difference between the type or number of stents placed, stent diameter, or concomitant celiac artery intervention between both groups. CONCLUSIONS: The natural history of SMA and multimodality defined ISR in CMI has not previously been described. Elevated PSV was a poor predictor of symptoms recurrence. Both asymptomatic and symptomatic patients with ISR did not differ in type of stent placed, time to ISR, or involvement of celiac artery. Antiplatelet use pre- and postoperatively appears protective against symptoms recurrence. Our findings underscore the need for long-term surveillance integrating clinical evaluation and multimodality imaging when indicated.

Management of patients with chronic mesenteric ischemia across three consecutive eras.

BACKGROUND: Endovascular intervention (EI) is the most commonly used modality for chronic mesenteric ischemia (CMI). Since the inception of this technique, numerous publications have reported the associated clinical outcomes. However, no publication has reported the comparative outcomes over a period of time in which both the stent platform and adjunctive medical therapy have evolved. This study aims to assess the impact of the concomitant evolution of both the endovascular approach and optimal guideline-directed medical therapy (GDMT) on CMI outcomes over three consecutive time eras. METHODS: A retrospective review at a quaternary center from January 2003 to August 2020 was performed to identify patients who underwent EIs for CMI. The patients were divided into three groups based on the date of intervention: early (2003-2009), mid (2010-2014), and late (2015-2020). At least one angioplasty/stent was performed for the superior mesenteric artery (SMA) and/or celiac artery. The patients' short- and mid-term outcomes were compared between the groups. Univariable and multivariable Cox proportional hazard models were also conducted to evaluate the clinical predictors for primary patency loss in SMA only subgroup. RESULTS: A total of 278 patients were included (early, 74; mid, 95; late, 109). The overall mean age was 71 years, and 70% were females. High technical success (early, 98.6%; mid, 100%; late, 100%; P = .27) and immediate resolution of symptoms (early, 86.3%; mid, 93.7%; late, 90.8%; P = .27) were noted over the three eras. In both the celiac artery and SMA cohorts, the use of bare metal stents (BMS) declined over time (early, 99.0%; mid, 90.3%; late, 65.5%; P < .001) with a proportionate increase in covered stents (CS) (early, 0.99%; mid, 9.7%; late, 28.9%; P < .001). The use of postoperative antiplatelet and statins has increased over time (early, 89.2%; mid, 97.9%; late, 99.1%; P = .003) and (early, 47%; mid, 68%; late, 81%; P = .001), respectively. In the SMA stent-only cohort, no significant differences were noted in primary patency rates between BMS and CS (hazard ratio, 0.95; 95% confidence interval, 0.26-2.87; P = .94). High-intensity preoperative statins were associated with fewer primary patency loss events compared to none/low- or moderate-intensity statins (hazard ratio, 0.30; 95% confidence interval, 0.11-0.72; P = .014). CONCLUSIONS: Consistent outcomes were observed for CMI EIs across three consecutive eras. In the SMA stent-only cohort, no statistically significant difference in early primary patency was noted for CS and BMS, making the use of CS at additional cost controversial and possibly not cost effective. Notably, the preoperative high-intensity statins were associated with improved SMA primary patency. These findings demonstrate the importance of guideline-directed medical therapy as an essential adjunct to EI in the treatment of CMI.

Predictors for Distal Revascularization Following Femoral Endarterectomy in Chronic Limb-Threatening Ischemia Patients.

OBJECTIVE: This study aims to identify the clinical variables which are predictive for the benefit of concomitant distal revascularization (DR) to prevent Chronic limb-threatening ischemia (CLTI) progression and the need for major limb amputation. METHODS: This is a retrospective cohort study of patients who presented with lower limb ischemia and required at least femoral endarterectomy (FEA), recruited over a period of 15 years (2002-2016). The patient cohort was divided into three groups based on the type of intervention: A (FEA alone), B (FEA + catheter-based intervention/(CBI)), and C (FEA + surgical bypass (SB)). The primary endpoint was to identify independent predictors for the use of concomitant DR (CBI or SB). Secondary endpoints were amputation rate, length of stay, mortality rate, postoperative ankle-brachial index and complications, readmission rate, re-intervention rate, resolution of symptoms and wound status. RESULTS: A total of 400 patients were included, 68.0% were males. Most presenting limbs were at Rutherford class (RC) III and WIfI stage 2, with an ankle-brachial index (ABI) of .47 ± .21 and a TASC II class C lesion. No significant differences were found in the primary-assisted and secondary patency rates between the three groups (P > .05, in all). In the multivariate analyses, clinical variables associated with DR were hyperlipidemia (hazard ratio (HR) 2.1-2.2), TASC II D (HR 2.62), Rutherford class 4 (HR 2.3) and 5 (HR 3.7), as well as WIfI stage ≥3 (HR 1.48). CONCLUSIONS: Femoral endarterectomy is sufficient to treat intermittent claudication. However, patients in whom rest pain, tissue loss or TASC II D anatomic lesion severity are present may benefit from concomitant distal revascularization. Taking into consideration the overall assessment of operative risk factors for each individual patient, proceduralists should have a lower threshold for performing early or concomitant distal revascularization to reduce CLTI progression including additional tissue loss and/or major limb amputation.

Novel fondaparinux protocol for anticoagulation therapy in adults with renal failure and suspected heparin-induced thrombocytopenia: a retrospective review of institutional protocol.

INTRODUCTION: The literature recommends against the use of fondaparinux in patients with kidney failure and dialysis as it may, with repeated dosing, accumulate and put patients at risk of bleeding. The management of patients with thrombosis in the presence of heparin-induced thrombocytopenia HIT requires the introduction of an alternative anticoagulant like bivalirudin or argatroban. When these drugs are not available, fondaparinux, remains the only alternative. In similar scenarios, there are few studies addressing how to administer it.  METHODS: We developed a protocol for fondaparinux in patients with renal failure where pharmacokinetic parameters are altered, and levels changed only after hemodialysis or in cases of residual renal activity. Patients received a full first dose except for high risk of bleeding. We targeted a peak anti-factor Xa activity level of 0.6-1.3 units/ml and changed the subsequent dose accordingly. Furthermore, we monitored the patients for signs of bleeding, a drop in hemoglobin level, or clinical signs of thrombosis.  DISCUSSION: We described 10 patients with kidney failure and suspected HIT taking fondaparinux. All the patients achieved therapeutic anti-factor Xa activity levels. However, one developed new-onset venous thromboembolism (VTE) despite therapeutic anti-factor Xa levels. Another patient experienced a bleeding episode. We believe that these two patients developed complications due to their medical conditions rather than the use of fondaparinux. CONCLUSION: Fondaparinux can be safely used in kidney failure using our protocol. However, despite its safety profile and relative success, this case series was small. More robust studies need to be conducted prior to drawing conclusions.

New Fondaparinux Protocol to Reduce the Risk of Blood Thickening and Blood Clots Formation in Adults with Kidney Disease and Heparin-induced Thrombocytopenia (drop in platelets after the use of heparin): A Test Study.Fondaparinux is a drug used to treat patients suffering from thrombosis (clot in blood) and prevent vessels occlusions. When patients have kidney disease, the ideal treatment for thrombosis would be heparin; and, in case of Heparin Induced Thrombocytopenia (HIT), an unexpected drop in platelets after the use of heparin, the ideal treatment would be argatroban or bivalirudin. Fondaparinux can be used for HIT. However, studies recommend against its use in kidney disease as it might accumulate and cause bleeding.We were put in a challenging situation where we had patients with life-threatening thrombosis, kidney disease, HIT and unavailability of both argatroban and bivalirudin. Our only option was fondaparinux. We had to devise a safe and efficient protocol. The starting dose was the one used had the patient had a normal kidney function. Then, anti-Factor Xa activity was regularly measured with the target level 0.6-1.3units/ml 4 h after a dose. The dose was individualized, changed based on the Factor Xa activity result, the risk of bleeding or thrombosis, the overall kidney function and the need for dialysis.Our protocol was tested on 10 patients. All our patients could reach the target and safe Factor Xa activity. We had 2 exceptions. The first had a clotting event despite having therapeutic Factor Xa activity and the second was a very sick cancer patient who was bleeding despite skipping many doses of fondaparinux. We consider that these 2 cases developed complications due to their medical conditions rather than the use of fondaparinux.We concluded that fondaparinux can be safely used in patients with kidney disease, granted that Factor Xa activity is measured, the risk of bleeding is weighed to the risk of thrombosis and the dose is individualized. However, our sample size is small and further studies with a larger number of patients are needed to draw a conclusion.

Vascular surgery integrated resident selection criteria in the pass or fail era.

OBJECTIVES: Vascular surgery integrated residency (VSIR) programs are highly competitive; however, criteria for resident selection remain opaque and non-standardized. The already unclear selection criteria will be further impacted by the impending transition of the United States Medical Licensing Examination (USMLE) Step 1 from numeric scores to a binary pass/fail outcome. The purpose of this study was to investigate the historical and anticipated selection criteria of VSIR applicants. METHODS: This was a cross-sectional, nationwide, 59-item survey that was sent to all VSIR program directors (PDs). Data was analyzed using the Fisher exact test if categorical and the Mann-Whitney U test and the Kruskal-Wallis test if ordinal. RESULTS: Forty of 69 PDs (58%) responded to the survey. University-based programs constituted 85% of responders. Most VSIR PDs (65%) reported reviewing between 101 to 150 applications for 1 to 2 positions annually. Forty-two percent of the responding PDs reported sole responsibility for inviting applicants to interview, whereas 50% had a team of faculty responsible for reviewing applications. On a five-point Likert scale, letters of recommendation (LOR) from vascular surgeons or colleagues (a person the PD knows) were the most important objective criteria. Work within a team structure was rated highest among subjective criteria. The majority of respondents (72%) currently use the Step 1 score as a primary method to screen applicants. Regional differences in use of Step 1 score as a primary screening method were: Midwest (100%), Northeast (76%), South (43%), and West (40%) (P = .01). PDs responded that that they will use USMLE Step 2 score (42%) and LOR (10%) to replace USMLE Step 1 score. The current top ranked selection criteria are letters from a vascular surgeon, USMLE Step 1 score and overall LOR. The proposed top ranked selection criteria after transition of USMLE Step 1 to pass/fail include LOR overall followed by Step 2 score. CONCLUSIONS: This is the first study to evaluate the selection criteria used by PDs for VSIR. The landscape of VSIR selection criteria is shifting and increasing transparency is essential to applicants' understanding of the selection process. The transition of USMLE Step 1 to a pass/fail report will shift the attention to Step 2 scores and elevate the importance of other relatively more subjective criteria. Defining VSIR program selection criteria is an important first step toward establishing holistic review processes that are transparent and equitable.

Isolated Superior Mesenteric Artery Dissection: A Novel Etiology and a Review.

Isolated superior mesenteric artery dissection (ISMAD) is a rare pathology with multifactorial etiology. The aim of this article is to provide a narrative review of the latest literature about ISMAD. Case reports, series, and recent meta-analyses were included. This review is introduced with a brief case report of a rare etiology of ISMAD, followed by a discussion of its etiology, clinical presentation, diagnosis, classification, and treatment, and we report a new cause of ISMAD, that is, blunt abdominal trauma. The etiology of ISMAD is multifactorial, consisting of anatomic, genetic, and systemic components. ISMAD is more common among middle-aged males and in East Asia. Its clinical presentation ranges from asymptomatic to mesenteric ischemia, albeit mortality remains <1%. It is diagnosed and classified mostly by computed tomography angiography, and there are five classification systems for ISMAD, though traumatic etiology may be added. The treatment of ISMAD is mostly conservative, with a success rate exceeding 90%. Endovascular stenting is second line, reserved so far for failed medical management, though its role is expanding to include earlier management of symptomatic patients, while open surgical repair is left for acute mesenteric ischemia with bowel compromise.

Medicine in Unplanned Mass Gatherings: A Qualitative Study of Health-Care Providers' Response and Recommendations to Beirut's Protests.

OBJECTIVE: This study aims at exploring the dynamics of health-care provision during recent unplanned public mass gatherings in Beirut, and how the health-care system adapts to mass movements in protests. METHODS: A qualitative study was conducted using semi-structured interviews with 12 health-care providers who volunteered at medical tents set during protests in Beirut, Lebanon. Responses were transcribed and coded. RESULTS: Three themes were noted: preparedness and logistics, encountered cases, and participants' proposed recommendations. In terms of preparedness and logistics, participants lacked knowledge of field medicine protocols and an organizational structure. They faced difficulties in securing equipment and advertising their services. Most encountered cases were physical injuries rather than mental health problems. The participants proposed both short-term recommendations, including advice on how to boost care provided, and long-term recommendations on structuring the health-care system to be better prepared. CONCLUSIONS: On-site health-care provision during unplanned mass gatherings is a vital need. We recommend forming a task force of health-care workers from various fields led by the Ministry of Public Health in every respective country to plan protocols, train personnel, and secure resources beforehand.

Management of dual traumatic arterial-venous fistula from a single shotgun injury: a case report and literature review.

BACKGROUND: Traumatic arteriovenous fistula (TAVF) is an uncommon vascular entity that arises in various locations, often from penetrating injuries, with a wide spectrum of signs and symptoms. This case report highlights the importance of suspecting multiple TAVFs after a single gunshot wound, especially if it involves pellets. It also sheds light on adapting treatment, whether endovascular or open repair, to the location and characteristics of each fistula. CASE PRESENTATION: A 35-year-old male, with history of shotgun wound 5 months earlier, presented to our clinic with right lower extremity (RLE) edema and pain. Arterial duplex scan and subsequent angiogram showed two TAVFs at the popliteal and posterior tibial (PT) arteries, both of which could not be exactly localized with a computed tomography angiography (CTA) due to artifacts. The fistula connecting the posterior tibial artery (PTA) and vein was repaired endovascularly using a covered-stent, while the fistula between the popliteal artery and vein was repaired surgically. Postoperative follow-up at 3 months showed no arteriovenous fistula (AVF), patent vessels and distal stent stenosis at the PTA. CONCLUSIONS: Patients who sustain gunshot injuries with shrapnel or pellets and develop TAVF consequentially need to be followed up with the possibility of multiple AVFs in mind. Arterial duplex scan is highly sensitive to detect those AVFs, yet angiography remains gold standard, particularly with extensive metal artefacts. Endovascular repair, when feasible, should be considered first, unless the patient is unstable or has anatomical constraints that increase the risk of complications. Lastly, surgeons should be weary of deep venous thrombosis (DVT), the Branham effect and arterial aneurysmal dilation postoperatively.

Presentation of intestinal malrotation and midgut volvulus in adults: Case report & literature review.

INTRODUCTION: Malrotation is considered a newborn disease. This case report sheds light on the rare, but possible late presentation of malrotation in adulthood, which if missed, can leave the patient in a detrimental state. PRESENTATION OF CASE: 28-year-old female presented in critical state with acute abdomen. Computed tomography abdomen/pelvis showed midgut volvulus, requiring urgent laparotomy. The patient's bowels were discolored, yet they normalized upon detorsion, except for a small portion, which was equivocal and left for observation. Ladd's bands were excised, and the abdomen was closed with Bogota bag for re-exploration. The patient underwent two more laparotomies to observe the intestinal segment until it was back to normal. Ladd procedure was then completed, and an absorbable mesh was applied. Follow-up of 20 months has been uneventful, except for a small, asymptomatic, incisional hernia. DISCUSSION: Malrotation in adults is often missed due to its subacute, nonspecific presentation. It is often diagnosed by CT abdomen, which shows inversion or vertical positioning of the superior mesenteric vessels. Symptomatic, but stable patients, can undergo laparoscopic Ladd procedure, which carries the benefit of less length of stay. While an incidental malrotation can be prophylactically operated on, correcting asymptomatic malrotation beyond age of 20 is ineffective and possibly harmful. CONCLUSION: Intestinal malrotation presenting in an adult should be on the differential diagnosis when dealing with abdominal pain, especially in the context of small bowel obstruction in a virgin abdomen. It is vital to consider a patient's age prior to prophylactically operate on malrotation discovered incidentally.

The hypertensive potential of estrogen: An untold story.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality worldwide. The implication of estrogen in this disease has been extensively studied. While the vast majority of published research argue for a cardioprotective role of estrogen in vascular inflammation such as in atherosclerosis, the role of estrogen in hypertension remains far from being resolved. The vasorelaxant effect of estrogen has already been well-established. However, emerging evidence supports a vasoconstrictive potential of this hormone. It has been proposed that the microenvironment dictates the effect of estrogen-induced type 1 nitric oxide synthase-1 (nNOS) on vasotone. Indeed, depending on nNOS product, nitric oxide or superoxide, estrogen can induce vasodilation or vasoconstriction, respectively. In this review, we discuss the evidence supporting the vasorelaxant effects of estrogen, and the molecular players involved. Furthermore, we shed light on recent reports revealing a vasoconstrictive role of estrogen, and speculate on the underlying signaling pathways. In addition, we identify certain factors that can account for the discrepant estrogenic effects. This review emphasizes a yin-yang role of estrogen in regulating blood pressure.

7-O-methylpunctatin, a Novel Homoisoflavonoid, Inhibits Phenotypic Switch of Human Arteriolar Smooth Muscle Cells.

Remodeling of arterioles is a pivotal event in the manifestation of many inflammation-based cardio-vasculopathologies, such as hypertension. During these remodeling events, vascular smooth muscle cells (VSMCs) switch from a contractile to a synthetic phenotype. The latter is characterized by increased proliferation, migration, and invasion. Compounds with anti-inflammatory actions have been successful in attenuating this phenotypic switch. While the vast majority of studies investigating phenotypic modulation were undertaken in VSMCs isolated from large vessels, little is known about the effect of such compounds on phenotypic switch in VSMCs of microvessels (microVSMCs). We have recently characterized a novel homoisoflavonoid that we called 7-O-methylpunctatin (MP). In this study, we show that MP decreased FBS-induced cell proliferation, migration, invasion, and adhesion. MP also attenuated adhesion of THP-1 monocytes to microVSMCs, abolished FBS-induced expression of MMP-2, MMP-9, and NF-κB, as well as reduced activation of ERK1/2 and FAK. Furthermore, MP-treated VSMCs showed an increase in early (myocardin, SM-22α, SM-α) and mid-term (calponin and caldesmon) differentiation markers and a decrease in osteopontin, a protein highly expressed in synthetic VSMCs. MP also reduced transcription of cyclin D1, CDK4 but increased protein levels of p21 and p27. Taken together, these results corroborate an anti-inflammatory action of MP on human microVSMCs. Therefore, by inhibiting the synthetic phenotype of microVSMCs, MP may be a promising modulator for inflammation-induced arteriolar pathophysiology.

Correction to: A Novel Somatic Variant in HEY2 Unveils an Alternative Splicing Isoform Linked to Ventricular Septal Defect.

The original version of this article unfortunately contained a mistake in the author name. The first author name should be Manal Fardoun instead of Manal Fardon. The original article has been corrected.

A Novel Somatic Variant in HEY2 Unveils an Alternative Splicing Isoform Linked to Ventricular Septal Defect.

Congenital heart defects (CHDs) are the leading cause of death in infants under 1 year of age. Aberrations in the expression and function of cardiac transcription factors (TFs) are a major contributor to CHDs. Despite the numerous studies undertaken to functionally characterize these TFs, their exact role in different stages of cardiogenesis is still not fully elucidated. Here we focused on HEY2, a basic helix loop helix transcriptional repressor, and its potential role in human ventricular septal defects. Genetic analysis was performed based on sequencing of DNA and cDNA obtained from post-operational cardiac tissues and blood of 17 Lebanese patients with various CHDs. The screen covered the entire coding regions of the GATA4, NKX2.5, TBX5, TBX20 and HEY2 genes. Our results revealed two novel somatic mutations, namely p.Ala229Thr and p.161_190 del, affecting HEY2 in the diseased cardiac tissues of two patients with VSD. These results suggest a potential role of HEY2 in regulating ventricular septation in humans.

MicroRNAs as Potential Pharmaco-targets in Ischemia-Reperfusion Injury Compounded by Diabetes.

BACKGROUND: Ischemia-Reperfusion (I/R) injury is the tissue damage that results from re-oxygenation of ischemic tissues. There are many players that contribute to I/R injury. One of these factors is the family of microRNAs (miRNAs), which are currently being heavily studied. This review aims to critically summarize the latest papers that attributed roles of certain miRNAs in I/R injury, particularly in diabetic conditions and dissect their potential as novel pharmacologic targets in the treatment and management of diabetes. METHODS: PubMed was searched for publications containing microRNA and I/R, in the absence or presence of diabetes. All papers that provided sufficient evidence linking miRNA with I/R, especially in the context of diabetes, were selected. Several miRNAs are found to be either pro-apoptotic, as in the case of miR-34a, miR-144, miR-155, and miR-200, or anti-apoptotic, as in the case of miR-210, miR-21, and miR-146a. Here, we further dissect the evidence that shows diverse cell-context dependent effects of these miRNAs, particularly in cardiomyocytes, endothelial, or leukocytes. We also provide insight into cases where the possibility of having two miRNAs working together to intensify a given response is noted. CONCLUSIONS: This review arrives at the conclusion that the utilization of miRNAs as translational agents or pharmaco-targets in treating I/R injury in diabetic patients is promising and becoming increasingly clearer.

Estrogen in vascular smooth muscle cells: A friend or a foe?

Cardiovascular disease (CVD) continues to be the leading cause of death worldwide. The effect of estrogen on these diseases has been assessed in in vitro and in vivo models, as well as in observational studies. Collectively, these studies alluded to a cardiovasculo-protective effect of estrogen. However, comprehensive clinical investigation failed to produce concrete proof of a cardiovascular protective effect for hormone replacement therapy (HRT), let alone rule out potential harm. These seemingly paradoxical effects of estrogen were explained by the 'theory of timing and opportunity'. This theory states that the effect of estrogen, whether cardiovasculo-protective or pathological, significantly depends on the age of the individual when estrogen administration takes place. Here, we review the conflicting effects of estrogen on vascular smooth muscle cells, mainly proliferation and migration as two cellular capacities intimately related to physiology and pathophysiology of the cardiovascular system. Furthermore, we critically discuss the major parameters and signaling pathways that may account for the aforementioned paradoxical observations, as well as the key molecular players involved.

The march of pluripotent stem cells in cardiovascular regenerative medicine.

Cardiovascular disease (CVD) continues to be the leading cause of global morbidity and mortality. Heart failure remains a major contributor to this mortality. Despite major therapeutic advances over the past decades, a better understanding of molecular and cellular mechanisms of CVD as well as improved therapeutic strategies for the management or treatment of heart failure are increasingly needed. Loss of myocardium is a major driver of heart failure. An attractive approach that appears to provide promising results in reducing cardiac degeneration is stem cell therapy (SCT). In this review, we describe different types of stem cells, including embryonic and adult stem cells, and we provide a detailed discussion of the properties of induced pluripotent stem cells (iPSCs). We also present and critically discuss the key methods used for converting somatic cells to pluripotent cells and iPSCs to cardiomyocytes (CMs), along with their advantages and limitations. Integrating and non-integrating reprogramming methods as well as characterization of iPSCs and iPSC-derived CMs are discussed. Furthermore, we critically present various methods of differentiating iPSCs to CMs. The value of iPSC-CMs in regenerative medicine as well as myocardial disease modeling and cardiac regeneration are emphasized.